@article{15048, abstract = {Embryogenesis results from the coordinated activities of different signaling pathways controlling cell fate specification and morphogenesis. In vertebrate gastrulation, both Nodal and BMP signaling play key roles in germ layer specification and morphogenesis, yet their interplay to coordinate embryo patterning with morphogenesis is still insufficiently understood. Here, we took a reductionist approach using zebrafish embryonic explants to study the coordination of Nodal and BMP signaling for embryo patterning and morphogenesis. We show that Nodal signaling triggers explant elongation by inducing mesendodermal progenitors but also suppressing BMP signaling activity at the site of mesendoderm induction. Consistent with this, ectopic BMP signaling in the mesendoderm blocks cell alignment and oriented mesendoderm intercalations, key processes during explant elongation. Translating these ex vivo observations to the intact embryo showed that, similar to explants, Nodal signaling suppresses the effect of BMP signaling on cell intercalations in the dorsal domain, thus allowing robust embryonic axis elongation. These findings suggest a dual function of Nodal signaling in embryonic axis elongation by both inducing mesendoderm and suppressing BMP effects in the dorsal portion of the mesendoderm.}, author = {Schauer, Alexandra and Pranjic-Ferscha, Kornelija and Hauschild, Robert and Heisenberg, Carl-Philipp J}, issn = {1477-9129}, journal = {Development}, number = {4}, pages = {1--18}, publisher = {The Company of Biologists}, title = {{Robust axis elongation by Nodal-dependent restriction of BMP signaling}}, doi = {10.1242/dev.202316}, volume = {151}, year = {2024}, } @article{14774, abstract = {Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.}, author = {Harish, Rohit K and Gupta, Mansi and Zöller, Daniela and Hartmann, Hella and Gheisari, Ali and Machate, Anja and Hans, Stefan and Brand, Michael}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology}, number = {19}, publisher = {The Company of Biologists}, title = {{Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation}}, doi = {10.1242/dev.201559}, volume = {150}, year = {2023}, } @article{12231, abstract = {Ventral tail bending, which is transient but pronounced, is found in many chordate embryos and constitutes an interesting model of how tissue interactions control embryo shape. Here, we identify one key upstream regulator of ventral tail bending in embryos of the ascidian Ciona. We show that during the early tailbud stages, ventral epidermal cells exhibit a boat-shaped morphology (boat cell) with a narrow apical surface where phosphorylated myosin light chain (pMLC) accumulates. We further show that interfering with the function of the BMP ligand Admp led to pMLC localizing to the basal instead of the apical side of ventral epidermal cells and a reduced number of boat cells. Finally, we show that cutting ventral epidermal midline cells at their apex using an ultraviolet laser relaxed ventral tail bending. Based on these results, we propose a previously unreported function for Admp in localizing pMLC to the apical side of ventral epidermal cells, which causes the tail to bend ventrally by resisting antero-posterior notochord extension at the ventral side of the tail.}, author = {Kogure, Yuki S. and Muraoka, Hiromochi and Koizumi, Wataru C. and Gelin-alessi, Raphaël and Godard, Benoit G and Oka, Kotaro and Heisenberg, Carl-Philipp J and Hotta, Kohji}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology}, number = {21}, publisher = {The Company of Biologists}, title = {{Admp regulates tail bending by controlling ventral epidermal cell polarity via phosphorylated myosin localization in Ciona}}, doi = {10.1242/dev.200215}, volume = {149}, year = {2022}, } @article{12245, abstract = {MicroRNAs (miRs) have an important role in tuning dynamic gene expression. However, the mechanism by which they are quantitatively controlled is unknown. We show that the amount of mature miR-9, a key regulator of neuronal development, increases during zebrafish neurogenesis in a sharp stepwise manner. We characterize the spatiotemporal profile of seven distinct microRNA primary transcripts (pri-mir)-9s that produce the same mature miR-9 and show that they are sequentially expressed during hindbrain neurogenesis. Expression of late-onset pri-mir-9-1 is added on to, rather than replacing, the expression of early onset pri-mir-9-4 and -9-5 in single cells. CRISPR/Cas9 mutation of the late-onset pri-mir-9-1 prevents the developmental increase of mature miR-9, reduces late neuronal differentiation and fails to downregulate Her6 at late stages. Mathematical modelling shows that an adaptive network containing Her6 is insensitive to linear increases in miR-9 but responds to stepwise increases of miR-9. We suggest that a sharp stepwise increase of mature miR-9 is created by sequential and additive temporal activation of distinct loci. This may be a strategy to overcome adaptation and facilitate a transition of Her6 to a new dynamic regime or steady state.}, author = {Soto, Ximena and Burton, Joshua and Manning, Cerys S. and Minchington, Thomas and Lea, Robert and Lee, Jessica and Kursawe, Jochen and Rattray, Magnus and Papalopulu, Nancy}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology}, number = {19}, publisher = {The Company of Biologists}, title = {{Sequential and additive expression of miR-9 precursors control timing of neurogenesis}}, doi = {10.1242/dev.200474}, volume = {149}, year = {2022}, } @article{7165, abstract = {Cell division, movement and differentiation contribute to pattern formation in developing tissues. This is the case in the vertebrate neural tube, in which neurons differentiate in a characteristic pattern from a highly dynamic proliferating pseudostratified epithelium. To investigate how progenitor proliferation and differentiation affect cell arrangement and growth of the neural tube, we used experimental measurements to develop a mechanical model of the apical surface of the neuroepithelium that incorporates the effect of interkinetic nuclear movement and spatially varying rates of neuronal differentiation. Simulations predict that tissue growth and the shape of lineage-related clones of cells differ with the rate of differentiation. Growth is isotropic in regions of high differentiation, but dorsoventrally biased in regions of low differentiation. This is consistent with experimental observations. The absence of directional signalling in the simulations indicates that global mechanical constraints are sufficient to explain the observed differences in anisotropy. This provides insight into how the tissue growth rate affects cell dynamics and growth anisotropy and opens up possibilities to study the coupling between mechanics, pattern formation and growth in the neural tube.}, author = {Guerrero, Pilar and Perez-Carrasco, Ruben and Zagórski, Marcin P and Page, David and Kicheva, Anna and Briscoe, James and Page, Karen M.}, issn = {1477-9129}, journal = {Development}, number = {23}, publisher = {The Company of Biologists}, title = {{Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium}}, doi = {10.1242/dev.176297}, volume = {146}, year = {2019}, } @article{7404, abstract = {The formation of neuronal dendrite branches is fundamental for the wiring and function of the nervous system. Indeed, dendrite branching enhances the coverage of the neuron's receptive field and modulates the initial processing of incoming stimuli. Complex dendrite patterns are achieved in vivo through a dynamic process of de novo branch formation, branch extension and retraction. The first step towards branch formation is the generation of a dynamic filopodium-like branchlet. The mechanisms underlying the initiation of dendrite branchlets are therefore crucial to the shaping of dendrites. Through in vivo time-lapse imaging of the subcellular localization of actin during the process of branching of Drosophila larva sensory neurons, combined with genetic analysis and electron tomography, we have identified the Actin-related protein (Arp) 2/3 complex as the major actin nucleator involved in the initiation of dendrite branchlet formation, under the control of the activator WAVE and of the small GTPase Rac1. Transient recruitment of an Arp2/3 component marks the site of branchlet initiation in vivo. These data position the activation of Arp2/3 as an early hub for the initiation of branchlet formation.}, author = {Stürner, Tomke and Tatarnikova, Anastasia and Müller, Jan and Schaffran, Barbara and Cuntz, Hermann and Zhang, Yun and Nemethova, Maria and Bogdan, Sven and Small, Vic and Tavosanis, Gaia}, issn = {1477-9129}, journal = {Development}, number = {7}, publisher = {The Company of Biologists}, title = {{Transient localization of the Arp2/3 complex initiates neuronal dendrite branching in vivo}}, doi = {10.1242/dev.171397}, volume = {146}, year = {2019}, } @article{12199, abstract = {The four microsporangia of the flowering plant anther develop from archesporial cells in the L2 of the primordium. Within each microsporangium, developing microsporocytes are surrounded by concentric monolayers of tapetal, middle layer and endothecial cells. How this intricate array of tissues, each containing relatively few cells, is established in an organ possessing no formal meristems is poorly understood. We describe here the pivotal role of the LRR receptor kinase EXCESS MICROSPOROCYTES 1 (EMS1) in forming the monolayer of tapetal nurse cells in Arabidopsis. Unusually for plants, tapetal cells are specified very early in development, and are subsequently stimulated to proliferate by a receptor-like kinase (RLK) complex that includes EMS1. Mutations in members of this EMS1 signalling complex and its putative ligand result in male-sterile plants in which tapetal initials fail to proliferate. Surprisingly, these cells continue to develop, isolated at the locular periphery. Mutant and wild-type microsporangia expand at similar rates and the ‘tapetal’ space at the periphery of mutant locules becomes occupied by microsporocytes. However, induction of late expression of EMS1 in the few tapetal initials in ems1 plants results in their proliferation to generate a functional tapetum, and this proliferation suppresses microsporocyte number. Our experiments also show that integrity of the tapetal monolayer is crucial for the maintenance of the polarity of divisions within it. This unexpected autonomy of the tapetal ‘lineage’ is discussed in the context of tissue development in complex plant organs, where constancy in size, shape and cell number is crucial.}, author = {Feng, Xiaoqi and Dickinson, Hugh G.}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology, Anther Tapetum, Arabidopsis, Cell Fate Establishment, EMS1, Reproductive Cell Lineage}, number = {14}, pages = {2409--2416}, publisher = {The Company of Biologists}, title = {{Tapetal cell fate, lineage and proliferation in the Arabidopsis anther}}, doi = {10.1242/dev.049320}, volume = {137}, year = {2010}, } @article{9524, abstract = {Cytosine methylation is the most common covalent modification of DNA in eukaryotes. DNA methylation has an important role in many aspects of biology, including development and disease. Methylation can be detected using bisulfite conversion, methylation-sensitive restriction enzymes, methyl-binding proteins and anti-methylcytosine antibodies. Combining these techniques with DNA microarrays and high-throughput sequencing has made the mapping of DNA methylation feasible on a genome-wide scale. Here we discuss recent developments and future directions for identifying and mapping methylation, in an effort to help colleagues to identify the approaches that best serve their research interests.}, author = {Zilberman, Daniel and Henikoff, Steven}, issn = {1477-9129}, journal = {Development}, number = {22}, pages = {3959--3965}, publisher = {The Company of Biologists}, title = {{Genome-wide analysis of DNA methylation patterns}}, doi = {10.1242/dev.001131}, volume = {134}, year = {2007}, } @article{4209, abstract = {We have identified widerborst (wdb), a B' regulatory subunit of PP2A, as a conserved component of planar cell polarization mechanisms in both Drosophila and in zebrafish. In Drosophila, wdb acts at two steps during planar polarization of wing epithelial cells. It is required to organize tissue polarity proteins into proximal and distal cortical domains, thus determining wing hair orientation. It is also needed to generate the polarized membrane outgrowth that becomes the wing hair. Widerborst activates the catalytic subunit of PP2A and localizes to the distal side of a planar microtubule web that lies at the level of apical cell junctions. This suggests that polarized PP2A activation along the planar microtubule web is important for planar polarization. In zebrafish, two wdb homologs are required for convergent extension during gastrulation, supporting the conjecture that Drosophila planar cell polarization and vertebrate gastrulation movements are regulated by similar mechanisms.}, author = {Hannus, Michael and Feiguin, Fabian and Heisenberg, Carl-Philipp J and Eaton, Suzanne}, issn = {0950-1991}, journal = {Development}, number = {14}, pages = {3493 -- 3503}, publisher = {Company of Biologists}, title = {{Planar cell polarization requires Widerborst, a B′ regulatory subunit of protein phosphatase 2A}}, doi = {10.1242/dev.129.14.3493}, volume = {129}, year = {2002}, } @article{4204, abstract = {During the development of the zebrafish nervous system both noi, a zebrafish pax2 homolog, and ace, a zebrafish fgf8 homolog, are required for development of the midbrain and cerebellum. Here we describe a dominant mutation, aussicht (aus), in which the expression of noi and ace is upregulated, In aus mutant embryos, ace is upregulated at many sites in the embryo, while Itoi expression is only upregulated in regions of the forebrain and midbrain which also express ace. Subsequent to the alterations in noi and ace expression, aus mutants exhibit defects in the differentiation of the forebrain, midbrain and eyes. Within the forebrain, the formation of the anterior and postoptic commissures is delayed and the expression of markers within the pretectal area is reduced. Within the midbrain, En and wnt1 expression is expanded. In heterozygous aus embryos, there is ectopic outgrowth of neural retina in the temporal half of the eyes, whereas in putative homozygous aus embryos, the ventral retina is reduced and the pigmented retinal epithelium is expanded towards the midline, The observation that ans mutant embryos exhibit widespread upregulation of ace raised the possibility that aus might represent an allele of the ace gene itself. However, by crossing carriers for both aus and ace, we were able to generate homozygous ace mutant embryos that also exhibited the aus phenotype, This indicated that aus is not tightly linked to ace and is unlikely to be a mutation directly affecting the ace locus. However, increased Ace activity may underly many aspects of the aus phenotype and we show that the upregulation of noi in the forebrain of aus mutants is partially dependent upon functional Ace activity. Conversely, increased ace expression in the forebrain of arcs mutants is not dependent upon functional Noi activity. We conclude that aus represents a mutation involving a locus normally required for the regulation of ace expression during embryogenesis.}, author = {Heisenberg, Carl-Philipp J and Brennan, Caroline and Wilson, Stephen}, issn = {0950-1991}, journal = {Development}, number = {10}, pages = {2129 -- 2140}, publisher = {Company of Biologists}, title = {{Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development}}, doi = {10.1242/dev.126.10.2129}, volume = {126}, year = {1999}, } @article{4142, abstract = {Mutations giving rise to anatomical defects in the inner ear have been isolated in a large scale screen for mutations causing visible abnormalities in the zebrafish embryo (Haffter, P., Granato, M., Brand, M. et al. (1996) Development 123, 1-36). 58 mutants have been classified as having a primary ear phenotype; these fall into several phenotypic classes, affecting presence or size of the otoliths, size and shape of the otic vesicle and formation of the semicircular canals, and define at least 20 complementation groups. Mutations in seven genes cause loss of one or both otoliths, but do not appear to affect development of other structures within the ear. Mutations in seven genes affect morphology and patterning of the inner ear epithelium, including formation of the semicircular canals and, in some, development of sensory patches (maculae and cristae). Within this class, dog-eared mutants show abnormal development of semicircular canals and lack cristae within the ear, while in van gogh, semicircular canals fail to form altogether, resulting in a tiny otic vesicle containing a single sensory patch. Both these mutants show defects in the expression of homeobox genes within the otic vesicle. In a further class of mutants, ear size is affected while patterning appears to be relatively normal; mutations in three genes cause expansion of the otic vesicle, while in little ears and microtic, the ear is abnormally small, but still contains all five sensory patches, as in the wild type. Many of the ear and otolith mutants show an expected behavioural phenotype: embryos fail to balance correctly, and may swim on their sides, upside down, or in circles. Several mutants with similar balance defects have also been isolated that have no obvious structural ear defect, but that may include mutants with vestibular dysfunction of the inner ear (Granato, M., van Eeden, F. J. M., Schach, U. et al. (1996) Development, 123, 399-413,). Mutations in 19 genes causing primary defects in other structures also show an ear defect. In particular, ear phenotypes are often found in conjunction with defects of neural crest derivatives (pigment cells and/or cartilaginous elements of the jaw). At least one mutant, dog-eared, shows defects in both the ear and another placodally derived sensory system, the lateral line, while hypersensitive mutants have additional trunk lateral line organs.}, author = {Whitfield, Tanya and Granato, Michael and Van Eeden, Fredericus 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 Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, pages = {241 -- 254}, publisher = {Company of Biologists}, title = {{Mutations affecting development of the zebrafish inner ear and lateral line}}, doi = {10.1242/dev.123.1.241}, volume = {123}, year = {1996}, } @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}, }