@article{4151, abstract = {Jaws and branchial arches together are a basic, segmented feature of the vertebrate head, Seven arches develop in the zebrafish embryo (Danio rerio), derived largely from neural crest cells that form the cartilaginous skeleton, In this and the following paper we describe the phenotypes of 109 arch mutants, focusing here on three classes that affect the posterior pharyngeal arches, including the hyoid and five gill-bearing arches, In lockjaw, the hyoid arch is strongly reduced and subsets of branchial arches do not develop, Mutants of a large second class, designated the flathead group, lack several adjacent branchial arches and their associated cartilages. Five alleles at the flathead locus all lead to larvae that lack arches 4-6, Among 34 other flathead group members complementation tests are incomplete, but at least six unique phenotypes can be distinguished, These all delete continuous stretches of adjacent branchial arches and unpaired cartilages in the ventral midline, Many show cell death in the midbrain, from which some neural crest precursors of the arches originate, lockjaw and a few mutants in the flathead group, including pistachio, affect both jaw cartilage and pigmentation, reflecting essential functions of these genes in at least two neural crest lineages, Mutants of a third class, including boxer, dackel and pincher, affect pectoral fins and axonal trajectories in the brain, as well as the arches. Their skeletal phenotypes suggest that they disrupt cartilage morphogenesis in all arches, Our results suggest that there are sets of genes that: (1) specify neural crest cells in groups of adjacent head segments, and (2) function in common genetic pathways in a variety of tissues including the brain, pectoral fins and pigment cells as well as pharyngeal arches.}, author = {Schilling, Thomas and Piotrowski, Tatjana and Grandel, Heiner and Brand, Michael and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Beuchle, Dirk and Hammerschmidt, Matthias and Kane, Donald and Mullins, Mary and Van Eeden, Fredericus and Kelsh, Robert and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Odenthal, Jörg and Warga, Rachel and Trowe, Torsten and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {329 -- 344}, publisher = {Company of Biologists}, title = {{Jaw and branchial arch mutants in zebrafish I: Branchial arches}}, doi = {10.1242/dev.123.1.329}, volume = {123}, year = {1996}, } @article{4154, abstract = {As part of a large scale chemical mutagenesis screen of the zebrafish (Danio rerio) genome, we have identified 33 mutants with defects in hematopoiesis, Complementation analysis placed 32 of these mutants into 17 complementation groups, The allelism of the remaining 1 blood mutant is currently unresolved, We have categorized these blood mutants into four phenotypic classes based on analyses of whole embryos and isolated blood cells, as well as by in situ hybridization using the hematopoietic transcription factors GATA-1 and GATA-2, Embryos mutant for the gene moonshine have few if any proerythroblasts visible on the day circulation begins and normal erythroid cell differentiation is blocked as determined by staining for hemoglobin and GATA-1 expression, Mutations in five genes, chablis, frascati, merlot, retsina, thunderbird and two possibly unique mutations cause a progressive decrease in the number of blood cells during the first 5 days of development, Mutations in another seven genes, chardonnay, chianti, grenache, sauternes, weibherbst and zinfandel, and two additional mutations result in hypochromic blood cells which also decrease in number as development proceeds, Several of these mutants have immature cells in the circulation, indicating a block in normal erythroid development. The mutation in zinfandel is dominant, and 2-day old heterozygous carriers fail to express detectable levels of hemoglobin and have decreasing numbers of circulating cells during the first 5 days of development, Mutations in two genes, freixenet and yquem, result in the animals that are photosensitive with autofluorescent blood, similar to that found in the human congenital porphyrias, The collection of mutants presented here represent several steps required for normal erythropoiesis, The analysis of these mutants provides a powerful approach towards defining the molecular mechanisms involved in vertebrate hematopoietic development.}, author = {Ransom, David and Haffter, Pascal and Odenthal, Jörg and Brownlie, Alison and Vogelsang, Elisabeth and Kelsh, Robert and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Mullins, Mary and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {311 -- 319}, publisher = {Company of Biologists}, title = {{Characterization of zebrafish mutants with defects in embryonic hematopoiesis}}, doi = {10.1242/dev.123.1.311}, volume = {123}, year = {1996}, } @article{4156, abstract = {In a large scale screen for mutants that affect the early development of the zebrafish, 109 mutants were found that cause defects in the formation of the jaw and the more posterior pharyngeal arches, Here we present the phenotypic description and results of the complementation analysis of mutants belonging to two major classes: (1) mutants with defects in the mandibular and hyoid arches and (2) mutants with defects in cartilage differentiation and growth in all arches, Mutations in four of the genes identified during the screen show specific defects in the first two arches and leave the more posterior pharyngeal arches largely unaffected (schmerle, sucker, hoover and sturgeon). In these mutants ventral components of the mandibular and hyoid arches are reduced (Meckel's cartilage and ceratohyal cartilage) whereas dorsal structures (palato-quadrate and hyosymplectic cartilages) are of normal size or enlarged, Thus, mutations in single genes cause defects in the formation of first and second arch structures but also differentially affect development of the dorsal and ventral structures within one arch. In 27 mutants that define at least 8 genes, the differentiation of cartilage and growth is affected. In hammerhead mutants particularly the mesodermally derived cartilages are reduced, whereas jellyfish mutant larvae are characterized by a severe reduction of all cartilaginous elements, leaving only two pieces in the position of the ceratohyal cartilages. In all other mutant larvae all skeletal elements are present, but consist of smaller and disorganized chondrocytes. These mutants also exhibit shortened heads and reduced pectoral fins. In homozygous knorrig embryos, tumor-like outgrowths of chondrocytes occur along the edges of all cartilaginous elements. The mutants presented here may be valuable tools for elucidating the genetic mechanisms that underlie the development of the mandibular and the hyoid arches, as well as the process of cartilage differentiation.}, author = {Piotrowski, Tatjana and Schilling, Thomas and Brand, Michael and Jiang, Yunjin and Heisenberg, Carl-Philipp J and Beuchle, Dirk and Grandel, Heiner and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Warga, Rachel and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {345 -- 356}, publisher = {Company of Biologists}, title = {{Jaw and branchial arch mutants in zebrafish II: Anterior arches and cartilage differentiation}}, doi = {10.1242/dev.123.1.345}, volume = {123}, year = {1996}, } @article{4164, abstract = {In a large-scale screen for mutants with defects in embryonic development we identified 17 genes (65 mutants) specifically required for the development of xanthophores, We provide evidence that these genes are required for three different aspects of xanthophore development, (1) Pigment cell formation and migration (pfeffer and salt); (2) pigment synthesis (edison, yobo, yocca and brie) and (3) pigment translocation (esrom, tilsit and tofu). The number of xanthophore cells that appear in the body is reduced in embryos with mutations in the two genes, salt and pfeffer. In heterozygous and homozygous salt and pfeffer adults, the melanophore stripes are interrupted, indicating that xanthophore cells have an important function in adult melanophore pattern formation, Most other genes affect only larval pigmentation, In embryos mutant for edison, yobo, yocca and brie, differences in pteridine synthesis can be observed under UV light and by thin-layer chromatography. Homozygous mutant females of yobo show a recessive maternal effect, Embryonic development is slowed down and embryos display head and tail truncations, Xanthophores in larvae mutant in the three genes esrom, tilsit and tofu appear less spread out, In addition, these mutants display a defect in retinotectal axon pathfinding, These mutations may affect xanthophore pigment distribution within the cells or xanthophore cell shape, Mutations in seven genes affecting xanthophore pigmentation remain unclassified.}, author = {Odenthal, Jörg and Rossnagel, Karin and Haffter, Pascal and Kelsh, Robert and Vogelsang, Elisabeth and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Mullins, Mary and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {391 -- 398}, publisher = {Company of Biologists}, title = {{Mutations affecting xanthophore pigmentation in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.391}, volume = {123}, year = {1996}, } @article{4166, abstract = {In a large scale screen for mutants with defects in the embryonic development of the zebrafish we identified mutations in four genes, floating head (flh), memo (mom), no tail (ntl), and dec, that are required for early notochord formation. Mutations in flh and ntl have been described previously, while mom and doe are newly identified genes. Mutant mom embryos lack a notochord in the trunk, and trunk somites from the right and left side of the embryo fuse underneath the neural tube. In this respect morn appears similar to flh. In contrast, notochord precursor cells are present in both ntl and doc embryos. In order to gain a greater understanding of the phenotypes, we have analysed the expression of several axial mesoderm markers in mutant embryos of all four genes. In flh and mom, Ntl expression is normal in the germ ring and tailbud, while the expression of Nd and other notochord markers in the axial mesodermal region is disrupted. Nd expression is normal in doc embryos until early semitic stages, when there is a reduction in expression which is first seen in anterior regions of the embryo. This suggests a function for doc in the maintenance of ntl expression. Other notochord markers such as twist, sonic hedgehog and axial are not expressed in the axial mesoderm of ntl embryos, their expression parallels the expression of ntl in the axial mesoderm of mutant doc,flh and mom embryos, indicating that ntl is required for the expression of these markers. The role of doc in the expression of the notochord markers appears indirect via ntl. Floor plate formation is disrupted in most regions in flh and mom mutant embryos but is present in mutant ntl and doc embryos. In mutant embryos with strong ntl alleles the band of cells expressing floor plate markers is broadened. A similar broadening is also observed in the axial mesoderm underlying the floor plate of ntl embryos, suggesting a direct involvement of the notochord precursor cells in floor plate induction. Mutations in al of these four genes result in embryos lacking a horizontal myoseptum and muscle pioneer cells, both of which are thought to be induced by the notochord. These somite defects can be traced back to an impairment of the specification of the adaxial cells during early stages of development. Transplantation of wild-type cells into mutant doc embryos reveals that wild-type notochord cells are sufficient to induce horizontal myoseptum formation in the flanking mutant tissue. Thus dec, like flh and ntl, acts cell autonomously in the notochord. In addition to the four mutants with defects in early notochord formation, we have isolated 84 mutants, defining at least 15 genes, with defects in later stages of notochord development. These are listed in an appendix to this study.}, author = {Odenthal, Jörg and Haffter, Pascal and Vogelsang, Elisabeth and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Kelsh, Robert and Mullins, Mary and Warga, Rachel and Allende, Miguel and Weinberg, Eric and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {103 -- 115}, publisher = {Company of Biologists}, title = {{Mutations affecting the formation of the notochord in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.103}, volume = {123}, year = {1996}, } @article{4170, abstract = {We identified 6 genes that are essential for specifying ventral regions of the early zebrafish embryo, Mutations in these genes cause an expansion of structures normally derived from dorsal-lateral regions of the blastula at the expense of ventrally derived structures, A series of phenotypes of varied strengths is observed with different alleles of these mutants, The weakest phenotype is a reduction in the ventral tail fin, observed as a dominant phenotype of swirl, piggytail, and somitabun and a recessive phenotype of min fin, lost-a-fin and some piggytail alleles, With increasing phenotypic strength, the blood and pronephric anlagen are also reduced or absent, while the paraxial mesoderm and anterior neuroectoderm is progressively expanded, In the strong phenotypes, displayed by homozygous embryos of snailhouse, swirl and somitabun, the somites circle around the embryo and the midbrain region is expanded laterally, Several mutations in this group of genes are semidominant as well as recessive indicating a strong dosage sensitivity of the processes involved, Mutations in the piggytail gene display an unusual dominance that depends on both a maternal and zygotic heterozygous genotype, while somitabun is a fully penetrant dominant maternal-effect mutation, The similar and overlapping phenotypes of mutants of the 6 genes identified suggest that they function in a common pathway, which begins in oogenesis, but also depends on factors provided after the onset of zygotic transcription, presumably during blastula stages, This pathway provides ventral positional information, counteracting the dorsalizing instructions of the organizer, which is localized in the dorsal shield.}, author = {Mullins, Mary and Hammerschmidt, Matthias and Kane, Donald and Odenthal, Jörg and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kelsh, Robert and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {81 -- 93}, publisher = {Company of Biologists}, title = {{Genes establishing dorsoventral pattern formation in the zebrafish embryo: The ventral specifying genes}}, doi = {10.1242/dev.123.1.81}, volume = {123}, year = {1996}, } @article{4186, abstract = {Neural crest development involves cell-fate specification, proliferation, patterned cell migration, survival and differentiation, Zebrafish neural crest derivatives include three distinct chromatophores, which are well-suited to genetic analysis of their development, As part of a large-scale mutagenesis screen for embryonic/early larval mutations, we have isolated 285 mutations affecting all aspects of zebrafish larval pigmentation, By complementation analysis, we define 94 genes, We show here that comparison of their phenotypes permits classification of these mutations according to the types of defects they cause, and these suggest which process of neural crest development is probably affected, Mutations in eight genes affect the number of chromatophores: these include strong candidates for genes necessary for the processes of pigment cell specification and proliferation, Mutations in five genes remove part of the wild-type pigment pattern, and suggest a role in larval pigment pattern formation, Mutations in five genes show ectopic chromatophores in distinct sites, and may have implications for chromatophore patterning and proliferation, 76 genes affect pigment or morphology of one or more chromatophore types: these mutations include strong candidates for genes important in various aspects of chromatophore differentiation and survival, In combination with the embryological advantages of zebrafish, these mutations should permit cellular and molecular dissection of many aspects of neural crest development.}, author = {Kelsh, Robert and Brand, Michael and Jiang, Yunjin and Heisenberg, Carl-Philipp J and Lin, Shuo and Haffter, Pascal and Odenthal, Jörg and Mullins, Mary and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Kane, Donald and Warga, Rachel and Beuchle, Dirk and Vogelsang, Lisa and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {369 -- 389}, publisher = {Company of Biologists}, title = {{Zebrafish pigmentation mutations and the processes of neural crest development}}, doi = {10.1242/dev.123.1.369}, volume = {123}, year = {1996}, } @article{4188, abstract = {Epiboly, the enveloping of the yolk cell by the blastoderm, is the first zebrafish morphogenetic movement, We isolated four mutations that affect epiboly: half baked, avalanche, lawine and weg, Homozygous mutant embryos arrest the vegetal progress of the deep cells of the blastoderm; only the yolk syncytial layer of the yolk cell and the enveloping layer of the blastoderm reach the vegetal pole of the embryo, The mutations half baked, avalanche and lawine produce a novel dominant effect, termed a zygotic-maternal dominant effect: heterozygous embryos produced from heterozygous females slow down epiboly and accumulate detached cells over the neural tube; a small fraction of these mutant individuals are viable, Heterozygous embryos produced from heterozygous males crossed to homozygous wild-type females complete epiboly normally and are completely viable. Additionally, embryos heterozygous for half baked have an enlarged hatching gland, a partial dominant phenotype, The phenotypes of these mutants demonstrate that, for the spreading of cells during epiboly, the movement of the deep cells of the blastoderm require the function of genes that are not necessary for the movement of the enveloping layer or the yolk cell, Furthermore, the dominant zygotic-maternal effect phenotypes illustrate the maternal and zygotic interplay of genes that orchestrate the early cell movements of the zebrafish.}, author = {Kane, Donald and Hammerschmidt, Matthias and Mullins, Mary and Maischein, Hans and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kelsh, Robert and Odenthal, Jörg and Warga, Rachel and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {47 -- 55}, publisher = {Company of Biologists}, title = {{The zebrafish epiboly mutants}}, doi = {10.1242/dev.123.1.47 }, volume = {123}, year = {1996}, } @article{4189, abstract = {This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but conditionally lethal: mutant cells, most of which lyse, sometimes survive to become notochord, muscles, or, in rare cases, large neurons, all cell types which become postmitotic in the gastrula. Some of the genes of the early arrest group may be necessary for progression though the cell cycle; if so, the survival of early differentiating cells may be based on having their terminal mitosis before the zygotic requirement for these genes.}, author = {Kane, Donald and Maischein, Hans and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Warga, Rachel and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {57 -- 66}, publisher = {Company of Biologists}, title = {{The zebrafish early arrest mutants}}, doi = {10.1242/dev.123.1.57 }, volume = {123}, year = {1996}, } @article{4191, abstract = {In a screen for embryonic mutants in the zebrafish a large number of mutants were isolated with abnormal brain morphology, We describe here 26 mutants in 13 complementation groups that show abnormal development of large regions of the brain, Early neurogenesis is affected in white tail (wit), During segmentation stages, homozygous wit embryos display an irregularly formed neural keel, particularly in the hindbrain, Using a variety of molecular markers, a severe increase in the number of various early differentiating neurons can be demonstrated, In contrast, late differentiating neurons, radial glial cells and some nonneural cell types, such as the neural crest-derived melanoblasts, are much reduced, Somitogenesis appears delayed, In addition, very reduced numbers of melanophores are present posterior to the mid-trunk, The wit phenotype is reminiscent of neurogenic mutants in Drosophila, such as Notch or Delta, In mutant parachute (pac) embryos the general organization of the hindbrain is disturbed and many rounded cells accumulate loosely in the hindbrain and midbrain ventricles, Mutants in a group of 6 genes, snakehead(snk), natter (nat), otter (ott) fullbrain (ful) viper (vip) and white snake (wis) develop collapsed brain ventricles, before showing signs of general degeneration, atlantis (atl), big head (bid), wicked brain (win), scabland (sbd) and eisspalte (ele) mutants have different malformation of the brain folds, Some of them have transient phenotypes, and mutant individuals may grow up to adults.}, author = {Jiang, Yunjin and Brand, Michael and Heisenberg, Carl-Philipp J and Beuchle, Dirk and Furutani Seiki, Makoto and Kelsh, Robert and Warga, Rachel and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Kane, Donald and Mullins, Mary and Odenthal, Jörg and Van Eeden, Fredericus and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {205 -- 216}, publisher = {Company of Biologists}, title = {{Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.205}, volume = {123}, year = {1996}, } @article{4203, abstract = {We identified four zebrafish mutants with defects in forebrain induction and patterning during embryogenesis. The four mutants define three genes: masterblind (mbl), silverblick (slb), and knollnase (kas), In mbl embryos, the anterior forebrain acquires posterior forebrain characteristics: anterior structures such as the eyes, olfactory placodes and the telencephalon are missing, whereas the epiphysis located in the posterior forebrain is expanded, In slb embryos, the extension of the embryonic axis is initially delayed and eventually followed by a partial fusion of the eyes, Finally, in kas embryos, separation of the telencephalic primordia is incomplete and dorsal midline cells fail to form a differentiated roof plate, Analysis of the mutant phenotypes indicates that we have identified genes essential for the specification of the anterior forebrain (mbl), positioning of the eyes (slb) and differentiation of the roof plate (kas). In an appendix to this study we list mutants showing alterations in the size of the eyes and abnormal differentiation of the lenses.}, author = {Heisenberg, Carl-Philipp J and Brand, Michael and Jiang, Yunjin and Warga, Rachel and Beuchle, Dirk and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, pages = {191 -- 203}, publisher = {Company of Biologists}, title = {{Genes involved in forebrain development in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.191 }, volume = {123}, year = {1996}, } @article{4208, abstract = {We have identified several genes that are required for various morphogenetic processes during gastrulation and tail formation, Two genes are required in the anterior region of the body axis: one eyed pinhead (oep) and dir ty nose (dns). oep mutant embryos are defective in prechordal plate formation and the specification of anterior and ventral structures of the central nervous system, In dns mutants, cells of the prechordal plate, such as the prospective hatching gland cells, fail to specify. Two genes are required for convergence and extension movements. In mutant trilobite embryos, extension movements on the dorsal side of the embryo are affected, whereas in the formerly described spadetail mutants, for which two new alleles have been isolated, convergent movements of ventrolateral cells to the dorsal side are blocked. Two genes are required for the development of the posterior end of the body axis, In pipetail mutants, the tailbud fails to move ventrally on the yolk sac after germ ring closure, and the tip of the tail fails to detach from the yolk tube. Mutants in kugelig (kgg) do not form the yolk tube at the posterior side of the yolk sac.}, author = {Hammerschmidt, Matthias and Pelegri, Francisco and Mullins, Mary and Kane, Donald and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kelsh, Robert and Odenthal, Jörg and Warga, Rachel and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {143 -- 151}, publisher = {Company of Biologists}, title = {{Mutations affecting morphogenesis during gastrulation and tail formation in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.143}, volume = {123}, year = {1996}, } @article{4210, abstract = {Mutations causing a visible phenotype in the adult serve as valuable visible genetic markers in multicellular genetic model organisms such as Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana. In a large scale screen for mutations affecting early development of the zebrafish, we identified a number of mutations that are homozygous viable or semiviable. Here we describe viable mutations which produce visible phenotypes in the adult fish. These predominantly affect the fins and pigmentation, but also the eyes and body length of the adult. A number of dominant mutations caused visible phenotypes in the adult fish, Mutations in three genes, long fin, another long fin and wanda affected fin formation in the adult. Four mutations were found to cause a dominant reduction of the overall body length in the adult. The adult pigment pattern was found to be changed by dominant mutations in wanda, asterix, obelix, leopard, salz and pfeffer. Among the recessive mutations producing visible phenotypes in the homozygous adult, a group of mutations that failed to produce melanin was assayed for tyrosinase activity. Mutations in sandy produced embryos that failed to express tyrosinase activity. These are potentially useful for using tyrosinase as a marker for the generation of transgenic lines of zebrafish.}, author = {Haffter, Pascal and Odenthal, Jörg and Mullins, Mary and Lin, Shuo and Farrell, Michael and Vogelsang, Elisabeth and Haas, Fabian and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Kelsh, Robert and Hopkins, Nancy and Nüsslein Volhard, Christiane}, issn = {0043-5546}, journal = {Development Genes and Evolution}, number = {4}, pages = {260 -- 276}, publisher = {Springer}, title = {{Mutations affecting pigmentation and shape of the adult zebrafish}}, doi = {10.1007/s004270050051}, volume = {206}, year = {1996}, } @article{4211, abstract = {We describe two genes, dino and mercedes, which are required for the organization of the zebrafish body plan, In dine mutant embryos, the tail is enlarged at the expense of the head and the anterior region of the trunk, The altered expression patterns of various marker genes reveal that, with the exception of the dorsal most marginal zone, all regions of the early dine mutant embryo acquire more ventral fates, These alterations are already apparent before the onset of gastrulation, mercedes mutant embryos show a similar but weaker phenotype, suggesting a role in the same patterning processes. The phenotypes suggests that dine and mercedes are required for the establishment of dorsal fates in both the marginal and the animal zone of the early gastrula embryo, Their function in the patterning of the ventrolateral mesoderm and the induction of the neuroectoderm is similar to the function of the Spemann organizer in the amphibian embryo.}, author = {Hammerschmidt, Matthias and Pelegri, Francisco and Mullins, Mary and Kane, Donald and Van Eeden, Fredericus and Granato, Michael and Brand, Michael and Furutani Seiki, Makoto and Haffter, Pascal and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kelsh, Robert and Odenthal, Jörg and Warga, Rachel and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {95 -- 102}, publisher = {Company of Biologists}, title = {{Dino and Mercedes, two genes regulating dorsal development in the zebrafish embryo}}, doi = {10.1242/dev.123.1.95}, volume = {123}, year = {1996}, } @article{4212, abstract = {In a large-scale screen, we isolated mutants displaying a specific visible phenotype in embryos or early larvae of the zebrafish, Danio rerio. Males were mutagenized with ethylnitrosourea (ENU) and F-2 families of single pair matings between sibling F-l fish, heterozygous for a mutagenized genome, were raised. Egg lays were obtained from several crosses between F-2 siblings, resulting in scoring of 3857 mutagenized genomes. F-3 progeny were scored at the second, third and sixth day of development, using a stereomicroscope. In a subsequent screen, fixed embryos were analyzed for correct retinotectal projection. A total of 4264 mutants were identified. Two thirds of the mutants displaying rather general abnormalities were eventually discarded. We kept and characterized 1163 mutants. In complementation crosses performed between mutants with similar phenotypes, 894 mutants have been assigned to 372 genes. The average allele frequency is 2.4. We identified genes involved in early development, notochord, brain, spinal cord, somites, muscles, heart, circulation, blood, skin, fin, eye, otic vesicle, jaw and branchial arches, pigment pattern, pigment formation, gut, liver, motility and touch response. Our collection contains alleles of almost all previously described zebrafish mutants. From the allele frequencies and other considerations we estimate that the 372 genes defined by the mutants probably represent more than half of all genes that could have been discovered using the criteria of our screen. Here we give an overview of the spectrum of mutant phenotypes obtained, and discuss the limits and the potentials of a genetic saturation screen in the zebrafish.}, author = {Haffter, Pascal and Granato, Michael and Brand, Michael and Mullins, Mary and Hammerschmidt, Matthias and Kane, Donald and Odenthal, Jörg and Van Eeden, Fredericus and Jiang, Yunjin and Heisenberg, Carl-Philipp J and Kelsh, Robert and Furutani Seiki, Makoto and Vogelsang, Elisabeth and Beuchle, Dirk and Schach, Ursula and Fabian, Cosima and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {1 -- 36}, publisher = {Company of Biologists}, title = {{The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.1 }, volume = {123}, year = {1996}, } @article{4213, abstract = {Forty zebrafish mutants with localized or general neural degeneration are described. The onset and duration of degeneration and the distribution of ectopically dying cells are specific characteristics of each mutant, Mutants are classified into four groups by these parameters. Class I: late focal neural degeneration mutants, These 18 mutants have restricted cell death mainly in the tectum and the dorsal hindbrain after 36 hours, The degeneration does not spread and disappears at later stages of development. Class LI: early focal neural degeneration mutants. Ten mutants in this class exhibit transient restricted degeneration affecting mainly the diencephalon, the hindbrain and the spinal cord at 20 hours, The midbrain is less affected. The degeneration shifts to the dorsal diencephalon and the tectum at 36 hours. Class III: late spreading neural degeneration mutants. The 8 mutants in this class display a degeneration that is first seen in the tectum and subsequently spreads throughout the nervous system from 36 hours on. Class IV: early general neural degeneration mutants, This class of four mutants already shows overall cell degeneration in the nervous system at the 15-somite stage. Three of the class I mutants show a change in the pattern of gene expression in the anlage of a brain structure prior to the onset of degeneration. These results suggest that focal cell death may be a useful clue for the detection of early patterning defects of the vertebrate nervous system in regions devoid of visible landmarks.}, author = {Furutani Seiki, Makoto and Jiang, Yunjin and Brand, Michael and Heisenberg, Carl-Philipp J and Houart, Corinne and Beuchle, Dirk and Van Eeden, Fredericus and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {229 -- 239}, publisher = {Company of Biologists}, title = {{Neural degeneration mutants in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.229 }, volume = {123}, year = {1996}, } @article{4214, abstract = {Zebrafish embryos and larvae have stage-specific patterns of motility or locomotion, Two embryonic structures accomplish this behavior: the central nervous system (CNS) and skeletal muscles. To identify genes that are functionally involved in mediating and controlling different patterns of embryonic and larval motility, we included a simple touch response test in our zebrafish large-scale genetic screen, In total we identified 166 mutants with specific defects in embryonic motility. These mutants fall into 14 phenotypically distinct groups comprising at least 48 genes, Here we describe the various phenotypic groups including mutants with no or reduced motility, mechanosensory defective mutants, 'spastic' mutants, circling mutants and motor circuit defective mutants, In 63 mutants, defining 18 genes, striation of semitic muscles is reduced, Phenotypic analysis provides evidence that these 18 genes have distinct and consecutive functions during semitic muscle development. The genes sloth (slo) and frozen (fro) already act during myoblast differentiation, while 13 genes appear to function later, in the formation of myofibers and the organization of sarcomeres, Mutations in four other genes result in muscle-specific degeneration, 103 mutations, defining at least 30 genes, cause no obvious defects in muscle formation and may instead affect neuronal development. Analysis of the behavioral defects suggests that these genes participate in the diverse locomotion patterns observed, such as touch response, rhythmic tail movements, equilibrium control, or that they simply confer general motility to the animal, In some of these mutants specific defects in the developing nervous system are detected, Mutations in two genes, nevermind (nev) and macho (mao), affect axonal projection in the optic tectum, whereas axon formation and elongation of motorneurons are disrupted by mutations in the diwanka (diw) and the unplugged (unp) genes.}, author = {Granato, Michael and Van Eeden, Fredericus and Schach, Ursula and Trowe, Torsten and Brand, Michael and Furutani Seiki, Makoto and Haffter, Pascal and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, pages = {399 -- 413}, publisher = {Company of Biologists}, title = {{Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva}}, doi = {10.1242/dev.123.1.399}, volume = {123}, year = {1996}, } @article{4215, abstract = {In a screen for early developmental mutants of the zebrafish, we have identified mutations specifically affecting the internal organs, We identified 53 mutations affecting the cardiovascular system, Nine of them affect specific landmarks of heart morphogenesis. Mutations in four genes cause a failure in the fusion of the bilateral heart primordia, resulting in cardia bifida. In lonely atrium, no heart venticle is visible and the atrium is directly fused to the outflow tract. In the overlooped mutant, the relative position of the two heart chambers is distorted, The heart is enormously enlarged in the santa mutant, In two mutants, scotch tape and superglue, the cardiac jelly between the two layers of the heart is significantly reduced, We also identified a number of mutations affecting the function of the heart, The mutations affecting heart function can be subdivided into two groups, one affecting heart contraction and another affecting the rhythm of the heart beat. Among the contractility group of mutants are 5 with no heart beat at all and 15 with a reduced heart beat of one or both chambers, 6 mutations are in the rhythmicity group and specifically affect the beating pattern of the heart, Mutations in two genes, bypass and kurzschluss, cause specific defects in the circulatory system, In addition to the heart mutants, we identified 23 mutations affecting the integrity of the liver, the intestine or the kidney, In this report, we demonstrate that it is feasible to screen for genes specific for the patterning or function of certain internal organs in the zebrafish, The mutations presented here could serve as an entrypoint to the establishment of a genetic hierarchy underlying organogenesis.}, author = {Chen, Jaunian and Haffter, Pascal and Odenthal, Jörg and Vogelsang, Elisabeth and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Kelsh, Robert and Mullins, Mary and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, pages = {293 -- 302}, publisher = {Company of Biologists}, title = {{Mutations affecting the cardiovascular system and other internal organs in zebrafish}}, doi = {10.1242/dev.123.1.293}, volume = {123}, year = {1996}, } @article{4216, abstract = {Tissues of the dorsal midline of vertebrate embryos, such as notochord and floor plate, have been implicated in inductive interactions that pattern the neural tube and somites. In our screen for embryonic visible mutations in the zebrafish we found 113 mutations in more than 27 genes with altered body shape, often with additional defects in CNS development. We concentrated on a subgroup of mutations in ten genes (the midline-group) that cause defective development of the floor plate. By using floor plate markers, such as the signaling molecule sonic hedgehog, we show that the schmalspur (sur) gene is needed for early floor plate development, similar to one-eyed-pinhead (oep) and the previously described cyclops (eye) gene. In contrast to oep and cyc, sur embryos show deletions of ventral CNS tissue restricted to the mid- and hindbrain, whereas the forebrain appears largely unaffected. In the underlying mesendodermal tissue of the head, sur is needed only for development of the posterior prechordal plate, whereas oep and eye are required for both anterior and posterior prechordal plate development. Our analysis of sur mutants suggests that defects within the posterior prechordal plate may cause aberrant development of ventral CNS structures in the mid- and hindbrain. Later development of the floor plate is affected in mutant chameleon, you-too, sonic-you, iguana, detour, schmalkars and monorail embryos; these mutants often show additional defects in tissues that are known to depend on signals from notochord and floor plate, For example, sur, con, and yot mutants show reduction of motor neurons; median deletions of brain tissue are seen in sur, con and yot embryos; and eye, con, yet, igu and dtr mutants often show no or abnormal formation of the optic chiasm. We also find fusions of the ventral neurocranium for all midline mutants tested, which may reveal a hitherto unrecognized function of the midline in influencing differentiation of neural crest cells at their destination. As a working hypothesis, we propose that midline-group genes may act to maintain proper structure and inductive function of zebrafish midline tissues.}, author = {Brand, Michael and Heisenberg, Carl-Philipp J and Warga, Rachel and Pelegri, Francisco and Karlstrom, Rolf and Beuchle, Dirk and Picker, Alexander and Jiang, Yunjin and Furutani Seiki, Makoto and Van Eeden, Fredericus and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {129 -- 142}, publisher = {Company of Biologists}, title = {{Mutations affecting development of the midline and general body shape during zebrafish embryogenesis}}, doi = {10.1242/dev.123.1.129 }, volume = {123}, year = {1996}, } @article{4219, abstract = {Mutations in two genes affect the formation of the boundary between midbrain and hindbrain (MHB): no isthmus (noi) and acerebellar (ace), noi mutant embryos lack the MHB constriction, the cerebellum and optic tectum, as well as the pronephric duct. Analysis of noi mutant embryos with neuron-specific antibodies shows that the MHB region and the dorsal and ventral midbrain are absent or abnormal, but that the rostral hindbrain is unaffected with the exception of the cerebellum, Using markers that are expressed during its formation (eng, wnt1 and pax-b), we find that the MHB region is already misspecified in noi mutant embryos during late gastrulation. The tectum is initially present and later degenerates, The defect in ace mutant embryos is more restricted: MHB and cerebellum are absent, but a tectum is formed, Molecular organisation of the tectum and tegmentum is disturbed, however, since eng, wntl and pax-b marker gene expression is not maintained, We propose that noi and ace are required for development of the MHB region and of the adjacent mid- and hindbrain, which are thought to be patterned by the MHB region, Presence of pax-b RNA, and absence of pax-b protein, together with the observation of genetic linkage and the occurrence of a point mutation, show that noi mutations are located in the pax-b gene, pax-b is a vertebrate orthologue of the Drosophila gene paired, which is involved in a pathway of cellular interactions at the posterior compartment boundary in Drosophila, Our results confirm and extend a previous report, and show that at least one member of this conserved signalling pathway is required for formation of the boundary between midbrain and hindbrain in the zebrafish.}, author = {Brand, Michael and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Beuchle, Dirk and Lun, Klaus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Van Eeden, Fredericus and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {179 -- 190}, publisher = {Company of Biologists}, title = {{Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain}}, doi = {10.1242/dev.123.1.179 }, volume = {123}, year = {1996}, }