@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{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}, } @article{4220, abstract = {In the zebrafish, Danio rerio, a caudal and pectoral fin fold develop during embryogenesis. At larval stages the caudal fin fold is replaced by four different fins, the unpaired anal, dorsal and tail fins. In addition the paired pelvic fins are formed, We have identified a total of 118 mutations affecting larval fin formation, Mutations in 11 genes lead to abnormal morphology or degeneration of both caudal and pectoral fin folds, Most mutants survive to adulthood and form a surprisingly normal complement of adult fins, Mutations in nine genes result in an increased or reduced size of the pectoral fins, Interestingly, in mutants of one of these genes, dackel (dak), pectoral fin buds form initially, but later the fin epithelium fails to expand, Expression of sonic hedgehog mRNA in the posterior mesenchyme of the pectoral fin bud is initiated in dak embryos, but not maintained, Mutations in five other genes affect adult fin but not larval fin development, Two mutants, longfin (lof) and another longfin (alf) have generally longer fins. Stein und bein (sub) has reduced dorsal and pelvic fins, whereas finless (fls) and wanda (wan) mutants affect all adult fins, Finally, mutations in four genes causing defects in embryonic skin formation will be briefly reported.}, author = {Van Eeden, Fredericus and Granato, Michael and Schach, Ursula 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 Warga, Rachel and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {255 -- 262}, publisher = {Company of Biologists}, title = {{Genetic analysis of fin formation in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.255 }, volume = {123}, year = {1996}, } @article{4222, abstract = {Somitogenesis is the basis of segmentation of the mesoderm in the trunk and tail of vertebrate embryos, Two groups of mutants with defects in this patterning process have been isolated in our screen for zygotic mutations affecting the embryonic development of the zebrafish (Danio rerio), In mutants of the first group, boundaries between individual somites are invisible early on, although the paraxial mesoderm is present, Later, irregular boundaries between somites are present, Mutations infused somites (fss) and beamter (bea) affect all somites, whereas mutations in deadly seven (des), after eight (aei) and white tail (wit) only affect the more posterior somites, Mutants of all genes but wit are homozygous viable and fertile, Skeletal stainings and the expression pattern of myoD and snail1 suggest that anteroposterior patterning within individual somites is abnormal, In the second group of mutants, formation of the horizontal myoseptum, which separates the dorsal and ventral part of the myotome, is reduced, Six genes have been defined in this group (you-type genes), yea-too mutants show the most severe phenotype; in these the adaxial cells, muscle pioneers and the primary motoneurons are affected, in addition to the horizontal myoseptum. The horizontal myoseptum is also missing in mutants that lack a notochord. The similarity of the somite phenotype in mutants lacking the notochord and in the you-type mutants suggests that the genes mutated in these two groups are involved in a signaling pathway from the notochord, important for patterning of the somites.}, author = {Van Eeden, Fredericus and Granato, Michael and Schach, Ursula 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 Warga, Rachel and Allende, Miguel and Weinberg, Eric and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {153 -- 164}, publisher = {Company of Biologists}, title = {{Mutations affecting somite formation and patterning in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.153}, volume = {123}, year = {1996}, }