@article{21039, abstract = {Cellular plasticity, the ability of a differentiated cell to adopt another phenotypic identity, is restricted under basal conditions, but can be elicited upon damage. However, the molecular mechanism enabling such plasticity remains largely unexplored. Here, we report damage-induced cellular plasticity of secretory enteroendocrine cells (EEs) in the adult Drosophila midgut. Ionizing radiation induces EE fate conversion and activates stress-responsive programs in EE lineages, accompanied by the induction of the stress-inducible transcription factor Xrp1 and the cytokine gene upd3. Xrp1 and upd3 are both necessary for radiation-induced EE plasticity. Under basal conditions, EE-specific Xrp1 overexpression triggers ectopic expression of progenitor-specific genes, which is necessary for Xrp1 to drive EE plasticity. Our work identifies Xrp1 as a crucial regulator that coordinates damage-induced signaling and transcriptional reprogramming, enabling the reactivation of cellular plasticity in differentiated cells.}, author = {Qian, Qingyin and Nagai, Hiroki and Sanaki, Yuya and Hayashi, Makoto and Kimura, Kenichi and Nakajima, Yu Ichiro and Niwa, Ryusuke}, issn = {1477-9129}, journal = {Development}, number = {2}, publisher = {The Company of Biologists}, title = {{Xrp1 drives damage-induced cellular plasticity of enteroendocrine cells in the adult Drosophila midgut}}, doi = {10.1242/dev.205225}, volume = {153}, year = {2026}, } @article{20048, abstract = {During embryonic development, cell behaviors need to be tightly regulated in time and space. Yet how the temporal and spatial regulations of cell behaviors are interconnected during embryonic development remains elusive. To address this, we turned to zebrafish gastrulation, the process whereby dynamic cell behaviors generate the three principal germ layers of the early embryo. Here, we show that Hoxb cluster genes are expressed in a temporally collinear manner at the blastoderm margin, where mesodermal and endodermal (mesendoderm) progenitor cells are specified and ingress to form mesendoderm/hypoblast. Functional analysis shows that these Hoxb genes regulate the timing of cell ingression: under- or overexpression of Hoxb genes perturb the timing of mesendoderm cell ingression and, consequently, the positioning of these cells along the forming anterior-posterior body axis after gastrulation. Finally, we found that Hoxb genes control the timing of mesendoderm ingression by regulating cellular bleb formation and cell surface fluctuations in the ingressing cells. Collectively, our findings suggest that Hoxb genes interconnect the temporal and spatial pattern of cell behaviors during zebrafish gastrulation by controlling cell surface fluctuations.}, author = {Moriyama, Yuuta and Mitsui, Toshiyuki and Heisenberg, Carl-Philipp J}, issn = {1477-9129}, journal = {Development}, number = {12}, publisher = {The Company of Biologists}, title = {{Hoxb genes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation}}, doi = {10.1242/dev.204261}, volume = {152}, year = {2025}, } @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{17458, abstract = {Changes in gene dosage can have tremendous evolutionary potential (e.g. whole-genome duplications), but without compensatory mechanisms, they can also lead to gene dysregulation and pathologies. Sex chromosomes are a paradigmatic example of naturally occurring gene dosage differences and their compensation. In species with chromosome-based sex determination, individuals within the same population necessarily show ‘natural’ differences in gene dosage for the sex chromosomes. In this Review, we focus on the mammalian X chromosome and discuss recent new insights into the dosage-compensation mechanisms that evolved along with the emergence of sex chromosomes, namely X-inactivation and X-upregulation. We also discuss the evolution of the genetic loci and molecular players involved, as well as the regulatory diversity and potentially different requirements for dosage compensation across mammalian species.}, author = {Cecalev, Daniela and Vicoso, Beatriz and Galupa, Rafael}, issn = {1477-9129}, journal = {Development}, number = {15}, publisher = {The Company of Biologists}, title = {{Compensation of gene dosage on the mammalian X}}, doi = {10.1242/dev.202891}, volume = {151}, year = {2024}, } @article{18621, abstract = {During neural development, cellular adhesion is crucial for interactions among and between neurons and surrounding tissues. This function is mediated by conserved cell adhesion molecules, which are tightly regulated to allow for coordinated neuronal outgrowth. Here, we show that the proprotein convertase KPC-1 (homolog of mammalian furin) regulates the Menorin adhesion complex during development of PVD dendritic arbors in Caenorhabditis elegans. We found a finely regulated antagonistic balance between PVD-expressed KPC-1 and the epidermally expressed putative cell adhesion molecule MNR-1 (Menorin). Genetically, partial loss of mnr-1 suppressed partial loss of kpc-1, and both loss of kpc-1 and transgenic overexpression of mnr-1 resulted in indistinguishable phenotypes in PVD dendrites. This balance regulated cell-surface localization of the DMA-1 leucine-rich transmembrane receptor in PVD neurons. Lastly, kpc-1 mutants showed increased amounts of MNR-1 and decreased amounts of muscle-derived LECT-2 (Chondromodulin II), which is also part of the Menorin adhesion complex. These observations suggest that KPC-1 in PVD neurons directly or indirectly controls the abundance of proteins of the Menorin adhesion complex from adjacent tissues, thereby providing negative feedback from the dendrite to the instructive cues of surrounding tissues.}, author = {Ramirez, Nelson and Belalcazar, Helen M. and Rahman, Maisha and Trivedi, Meera and Tang, Leo T. H. and Bülow, Hannes E.}, issn = {1477-9129}, journal = {Development}, number = {18}, publisher = {The Company of Biologists}, title = {{Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion}}, doi = {10.1242/dev.201208}, volume = {150}, year = {2023}, } @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{15262, abstract = {The Hunchback (Hb) transcription factor is crucial for anterior-posterior patterning of the Drosophila embryo. The maternal hb mRNA acts as a paradigm for translational regulation due to its repression in the posterior of the embryo. However, little is known about the translatability of zygotically transcribed hb mRNAs. Here, we adapt the SunTag system, developed for imaging translation at single-mRNA resolution in tissue culture cells, to the Drosophila embryo to study the translation dynamics of zygotic hb mRNAs. Using single-molecule imaging in fixed and live embryos, we provide evidence for translational repression of zygotic SunTag-hb mRNAs. Whereas the proportion of SunTag-hb mRNAs translated is initially uniform, translation declines from the anterior over time until it becomes restricted to a posterior band in the expression domain. We discuss how regulated hb mRNA translation may help establish the sharp Hb expression boundary, which is a model for precision and noise during developmental patterning. Overall, our data show how use of the SunTag method on fixed and live embryos is a powerful combination for elucidating spatiotemporal regulation of mRNA translation in Drosophila.}, author = {Vinter, Daisy J. and Hoppe, Caroline and Minchington, Thomas and Sutcliffe, Catherine and Ashe, Hilary L.}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology}, number = {18}, publisher = {The Company of Biologists}, title = {{Dynamics of hunchback translation in real-time and at single-mRNA resolution in the Drosophila embryo}}, doi = {10.1242/dev.196121}, volume = {148}, year = {2021}, } @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{654, abstract = {In November 2016, developmental biologists, synthetic biologists and engineers gathered in Paris for a meeting called ‘Engineering the embryo’. The participants shared an interest in exploring how synthetic systems can reveal new principles of embryonic development, and how the in vitro manipulation and modeling of development using stem cells can be used to integrate ideas and expertise from physics, developmental biology and tissue engineering. As we review here, the conference pinpointed some of the challenges arising at the intersection of these fields, along with great enthusiasm for finding new approaches and collaborations.}, author = {Kicheva, Anna and Rivron, Nicolas}, issn = {0950-1991}, journal = {Development}, number = {5}, pages = {733 -- 736}, publisher = {Company of Biologists}, title = {{Creating to understand – developmental biology meets engineering in Paris}}, doi = {10.1242/dev.144915}, volume = {144}, year = {2017}, } @article{676, abstract = {The segregation of different cell types into distinct tissues is a fundamental process in metazoan development. Differences in cell adhesion and cortex tension are commonly thought to drive cell sorting by regulating tissue surface tension (TST). However, the role that differential TST plays in cell segregation within the developing embryo is as yet unclear. Here, we have analyzed the role of differential TST for germ layer progenitor cell segregation during zebrafish gastrulation. Contrary to previous observations that differential TST drives germ layer progenitor cell segregation in vitro, we show that germ layers display indistinguishable TST within the gastrulating embryo, arguing against differential TST driving germ layer progenitor cell segregation in vivo. We further show that the osmolarity of the interstitial fluid (IF) is an important factor that influences germ layer TST in vivo, and that lower osmolarity of the IF compared with standard cell culture medium can explain why germ layers display differential TST in culture but not in vivo. Finally, we show that directed migration of mesendoderm progenitors is required for germ layer progenitor cell segregation and germ layer formation.}, author = {Krens, Gabriel and Veldhuis, Jim and Barone, Vanessa and Capek, Daniel and Maître, Jean-Léon and Brodland, Wayne and Heisenberg, Carl-Philipp J}, issn = {0950-1991}, journal = {Development}, number = {10}, pages = {1798 -- 1806}, publisher = {Company of Biologists}, title = {{Interstitial fluid osmolarity modulates the action of differential tissue surface tension in progenitor cell segregation during gastrulation}}, doi = {10.1242/dev.144964}, volume = {144}, year = {2017}, } @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{4161, abstract = {Handedness of the vertebrate body plan critically depends on transient embryonic structures/ organs that generate cilia-dependent leftward fluid flow within constrained extracellular environments. Although the function of ciliated organs in laterality determination has been extensively studied, how they are formed during embryogenesis is still poorly understood. Here we show that Kupffer's vesicle (KV), the zebrafish organ of laterality, arises from a surface epithelium previously thought to adopt exclusively extra-embryonic fates. Live multi-photon confocal imaging reveals that surface epithelial cells undergo Nodal/TGF beta signalling-dependent ingression at the dorsal germ ring margin prior to gastrulation, to give rise to dorsal forerunner cells (DFCs), the precursors of KV. DFCs then migrate attached to the overlying surface epithelium and rearrange into rosette-like epithelial structures at the end of gastrulation. During early somitogenesis, these epithelial rosettes coalesce into a single rosette that differentiates into the KV with a ciliated lumen at its apical centre. Our results provide novel insights into the morphogenetic transformations that shape the laterality organ in zebrafish and suggest a conserved progenitor role of the surface epithelium during laterality organ formation in vertebrates.}, author = {Oteíza, Pablo and Köppen, Mathias and Concha, Miguel and Heisenberg, Carl-Philipp J}, issn = {1477-9129}, journal = {Development}, number = {16}, pages = {2807 -- 2813}, publisher = {Company of Biologists}, title = {{Origin and shaping of the laterality organ in zebrafish}}, doi = {10.1242/dev.022228}, volume = {135}, year = {2008}, } @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}, }