bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations affecting development of the zebrafish retina
Authors: Malicki Jarema , Neuhauss Stephan C. F. , Schier Alexander F. , Solnica-Krezel Lilianna , Stemple Derek L. , Stainier Didier Y. R , Abdelilah Salim , Zwartkruis Fried , Rangini Zehava , Driever Wolfgang 
Published: April 2021

ABSTRACT
In a large scale screen for genetic defects in zebrafish embryogenesis we identified 49 mutations affecting development of the retina. Based on analysis of living embryos as well as histological sections, we grouped the isolated mutations into six phenotypic categories. (1) Mutations in three loci result in a loss of wild-type laminar pattern of the neural retina. (2) Defects in four loci lead to an abnormal specification of the eye anlagen. Only one eye frequently forms in this class of mutants. (3) Seven loci predominantly affect development of the outer retinal layers. Mutants in this category display cell loss mainly in the photoreceptor cell layer. (4) Nine mutations cause retardation of eye growth without any other obvious abnormalities in the retina. (5) A group of twelve mutations is characterized by nonspecific retinal degeneration. (6) Four mutations display retinal degeneration associated with a pigmentation defect. Finally, two mutations, one with absence of the ventral retina and one with an eye-specific pigmentation defect, are not classified in any of the above groups. The identified mutations affect numerous aspects of eye development, including: specification of the eye anlage, growth rate of the optic cup, establishment of retinal stratification, specification or differentiation of retinal neurons and formation of the dorsoventral axis in the developing eye.
Mutations affecting development of the zebrafish ear
Authors: Malicki Jarema , Schier Alexander F. , Solnica-Krezel Lilianna , Stemple Derek L. , Neuhauss Stephan C. F. , Stainier Didier Y. R. , Abdelilah Salim , Rangini Zehava , Zwartkruis Fried , Driever Wolfgang 
Published: April 2021

ABSTRACT
In a large scale screen for genetic defects in zebrafish embryogenesis we identified mutations affecting several aspects of ear development, including: specification of the otic placode, growth of the otic vesicle (otocyst), otolith formation, morphogenesis of the semicircular canals and differentiation of the otic capsule. Here we report initial phenotypic and genetic characterization of 20 of these mutations defining 13 independent loci. Embryos mutant at the quadro locus display abnormal specification of the otic placode. As revealed by dlx-3 expression, the otic field in the mutant embryos is smaller or split into two fields. At later stages of development the ear of quadro mutants is frequently divided into two smaller, incomplete units. Four loci affect ear shape shortly after formation of the otic vesicle. All of them also display abnormal brain morphology. Mutations in five loci result in the absence of otolith formation; two of these also produce changes of ear morphology. Two loci, little richard and golas, affect morphology of the otic vesicle shortly before formation of the semicircular canals. In both cases the morphogenesis of the semicircular canals is disrupted. Finally, the antytalent locus is involved in late expansion of the ear structure. Analysis of mutations presented here will strengthen our understanding of vertebrate ear morphogenesis and provide novel entry points to its genetic analysis.
Hematopoietic mutations in the zebrafish
Authors: Weinstein Brant M. , Schier Alexander F. , Abdelilah Salim , Malicki Jarema , Solnica-Krezel Lilliana , Stemple Derek L. , Stainier Didier Y. R. , Zwartkruis Fried , Driever Wolfgang , Fishman Mark C. 
Published: April 2021

ABSTRACT
We have identified mutations that perturb the formation or differentiation of the first embryonic blood cells in the zebrafish embryo. These ‘primitive’ red blood cells originate in the intermediate cell mass of the trunk, a derivative of the dorsal lateral plate mesoderm. By transfusion of blood between embryos we demonstrate that this cohort of cells provides the embryo with all, or nearly all, of its blood cells until at least day 5 postfertilization. Larval lethal mutations generated by ENU mutagenesis affect different steps in the development of these cells. Some cause defects in precursor generation, others defects in differentiation, and others an increase in cellular photosensitivity.
Characterization of zebrafish mutants with defects in embryonic hematopoiesis
Authors: Ransom David G. , Haffter Pascal , Odenthal Jörg , Brownlie Alison , Vogelsang Elisabeth , Kelsh Robert N. , Brand Michael , Eeden Fredericus J. M. van , Furutani-Seiki Makoto , Granato Michael , Hammerschmidt Matthias , Heisenberg Carl-Phillip , Jiang Yun-Jin , Kane Donald A. , Mullins Mary C. , Nüsslein-Volhard Christiane 
Published: April 2021

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 hemoglo-bin 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, weißherbst 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.
Jaw and branchial arch mutants in zebrafish I: branchial arches
Authors: Schilling Thomas F. , Piotrowski Tatjana , Grandel Heiner , Brand Michael , Heisenberg Carl-Philipp , Jiang Yun-Jin , Beuchle Dirk , Hammerschmidt Matthias , Kane Donald A. , Mullins Mary C. , Eeden Fredericus J. M. van , Kelsh Robert N. , Furutani-Seiki Makoto , Granato Michael , Haffter Pascal , Odenthal Jörg , Warga Rachel M. , Trowe Torsten , Nüsslein-Volhard Christiane 
Published: April 2021

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.
Mutations affecting craniofacial development in zebrafish
Authors: Neuhauss Stephan C. F. , Solnica-Krezel Lilianna , Schier Alexander F. , Zwartkruis Fried , Stemple Derek L. , Malicki Jarema , Abdelilah Salim , Stainier Didier Y. R. , Driever Wolfgang 
Published: April 2021

ABSTRACT
In a large-scale screen for mutations affecting embryogenesis in zebrafish, we identified 48 mutations in 34 genetic loci specifically affecting craniofacial development. Mutants were analyzed for abnormalities in the cartilaginous head skeleton. Further, the expression of marker genes was studied to investigate potential abnormalities in mutant rhombencephalon, neural crest, and pharyngeal endoderm. The results suggest that the identified mutations affect three distinct aspects of craniofacial development. In one group, mutations affect the overall pattern of the craniofacial skeleton, suggesting that the genes are involved in the specification of these elements. Another large group of mutations affects differentiation and morphogenesis of cartilage, and may provide insight into the genetic control of chondrogenesis. The last group of mutations leads to the abnormal arrangement of skeletal elements and may uncover important tissue-tissue interactions underlying jaw development.
Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva
Authors: Granato Michael , Eeden Fredericus J. M. van , Schach Ursula , Trowe Torsten , Brand Michael , Furutani-Seiki Makoto , Haffter Pascal , Hammerschmidt Matthias , Heisenberg Carl-Philipp , Jiang Yun-Jin , Kane Donald A. , Kelsh Robert N. , Mullins Mary C. , Odenthal Jörg , Nüsslein-Volhard Christiane 
Published: April 2021

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 somitic muscles is reduced. Phenotypic analysis provides evidence that these 18 genes have distinct and consecutive functions during somitic 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 loco-motion 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.
Specification of the embryonic limb primordium by graded activity of Decapentaplegic
Authors: Goto Satoshi , Hayashi Shigeo 
Published: April 2021

ABSTRACT
Two thoracic limbs of Drosophila, the leg and the wing, originate from a common cluster of cells that include the source of two secreted signaling molecules, Decapentaplegic and Wingless. We show that Wingless, but not Decapentaplegic, is responsible for initial specification of the limb primordia with a distal identity. Limb formation is restricted to the lateral position of the embryo by negative control of the early function of Decapentaplegic and the EGF receptor homolog that determine the global dorsoventral pattern. Late function of Decapentaplegic locally determines two additional cell identities in a dosage dependent manner. Loss of Decapentaplegic activity results in a deletion of the proximal structures of the limb, which is in contrast to the consequence of decapentaplegic mutations in the imaginal disc, which cause a deletion of distal structures. The results indicate that the limb pattern elements are added in a distal to proximal direction in the embryo, which is opposite to what is happening in the growing imaginal disc. We propose that Wingless and Decapentaplegic act sequentially to initiate the proximodistal axis.
Planarian Hox genes: novel patterns of expression during regeneration
Authors: Bayascas J. R. , Castillo E. , Muñoz-Mármol A. M. , Saló E. 
Published: April 2021

ABSTRACT
Platyhelminthes are widely considered to be the sister group of coelomates (Philippe, H., Chenuil, A. and Adoutte, A. (1994)Development 1994 Supplement, 15-24) and the first organisms to show bilateral symmetry and cephalization. Within this phylum, the freshwater planarians (Turbellaria, Tricladida) have been used as model systems for studying bidirectional regeneration (Slack, J. M. W. (1980) J. Theor. Biol. 82, 105-140). We have been attempting to identify potential pattern-control genes involved in the regeneration of planarian heads and tails after amputation. Since Hox cluster genes determine positional identity along the anteroposterior axis in a wide range of animals (Slack, J. M. W., Holland, P. W. H. and Graham, C. F. (1993) Nature 361, 490-492), we performed an extensive search for Hox-related genes in the planarian Dugesia(G)tigrina. Sequence analyses of seven planarian Dthox genes (Dthox-A to Dthox-G) reveal high similarities with the homeodomain region of the Hox cluster genes, allowing us to assign planarian Dthox genes to anterior and medial Hox cluster paralogous groups. Whole-mount in situ hybridization studies in regenerating adults showed very early, synchronous and colocalized activation of Dthox-D, Dthox-A, Dthox-C, Dthox-E, Dthox-G and Dthox-F. After one hour of regeneration a clear expression was observed in all Dthox genes studied. In addition, all seemed to be expressed in the same regenerative tissue, although in the last stages of regeneration (9 to 15 days) a differential timing of deactivation was observed. The same Dthox genes were also expressed synchronously and were colocalized during intercalary regeneration, although their expression was delayed. Terminal regeneration showed identical Dthox gene expression in anterior and posterior blastemas, which may prevent these genes from directing the distinction between head and tail. Finally, continuous expression along the whole lateral blastema in sagittal regenerates reflected a ubiquitous Dthox response in all types of regeneration that was not related specifically with the anteroposterior polarity.
Sclerotome development and peripheral nervous system segmentation in embryonic zebrafish
Authors: Morin-Kensicki Elizabeth M. , Eisen Judith S. 
Published: April 2021

ABSTRACT
Vertebrate embryos display segmental patterns in many trunk structures, including somites and peripheral nervous system elements. Previous work in avian embryos suggests a role for somite-derived sclerotome in segmental patterning of the peripheral nervous system. We investigated sclerotome development and tested its role in patterning motor axons and dorsal root ganglia in embryonic zebrafish. Individual somite cells labeled with vital fluorescent dye revealed that some cells of a ventromedial cell cluster within each somite produced mesenchymal cells that migrated to positions expected for sclerotome. Individual somites showed anterior/posterior distinctions in several aspects of development: (1) anterior ventromedial cluster cells produced only sclerotome, (2) individual posterior ventromedial cluster cells produced both sclerotome and muscle, and (3) anterior sclerotome migrated earlier and along a more restricted path than posterior sclerotome. Vital labeling showed that anterior sclerotome colocalized with extending identified motor axons and migrating neural crest cells. To investigate sclerotome involvement in peripheral nervous system patterning, we ablated the ventromedial cell cluster and observed subsequent development of peripheral nervous system elements. Primary motor axons were essentially unaffected by sclerotome ablation, although in some cases outgrowth was delayed. Removal of sclerotome did not disrupt segmental pattern or development of dorsal root ganglia or peripheral nerves to axial muscle. We propose that peripheral nervous system segmentation is established through interactions with adjacent paraxial mesoderm which develops as sclerotome in some vertebrate species and myotome in others.
The Drosophila dCREB-A gene is required for dorsal/ventral patterning of the larval cuticle
Authors: Andrew Deborah J. , Baig Anjum , Bhanot Purnima , Smolik Sarah M. , Henderson Katya D. 
Published: April 2021

ABSTRACT
We report on the characterization of the first loss-of-function mutation in a Drosophila CREB gene, dCREB-A. In the epidermis, dCREB-A is required for patterning cuticular structures on both dorsal and ventral surfaces since dCREB-A mutant larvae have only lateral structures around the entire circumference of each segment. Based on results from epistasis tests with known dorsal/ventral patterning genes, we propose that dCREB-A encodes a transcription factor that functions near the end of both the DPP- and SPI-signaling cascades to translate the corresponding extracellular signals into changes in gene expression. The lateralizing phenotype of dCREB-A mutants reveals a much broader function for CREB proteins than previously thought.
Compartmental organization of the Drosophila genital imaginal discs
Authors: Chen Elizabeth H. , Baker Bruce S. 
Published: April 2021

ABSTRACT
We have investigated the anterior and posterior compartmental organization of the genital imaginal disc. Unlike the thoracic discs, the genital disc is a compound disc consisting of three primordia – the female genital, male genital, and anal primordia. Here we provide evidence that each primordium is divided into anterior and posterior compartments. Genes that are known to be expressed in compartment-specific manners in other discs (engrailed, hedgehog, patched, decapentaplegic, wingless and cubitus interruptus) are expressed in analogous patterns in each primordium of the genital disc. Specifically, engrailed and cubitus interruptus are expressed in complementary domains, while patched, decapentaplegic and wingless are expressed along the border between the two domains. Mitotic clones induced at the beginning of the second larval instar do not cross the boundary between the engrailed-expressing and cubitus interruptus-expressing domains, indicating that these domains are true genetic compartments. Furthermore, we examined the phenotypes of mutant clones of the cAMP-dependent protein kinase A and engrailed-invected, genes that are known to play compartment-specific functions in other discs. These experiments demonstrate that the anterior/posterior patterning functions of these genes are conserved in the genital disc. The adult clonal phenotypes of protein kinase A and engrailed-invected mutants also provide a more detailed map of the adult genitalia and analia with respect to the anterior/posterior compartmental subdivision. Our results lead us to propose a new model to describe the anterior and posterior compartmental organization of the genital disc.
Sperm-egg fusion is the prelude to the initial Ca2+ increase at fertilization in the mouse
Authors: Lawrence Yvonne , Whitaker Michael , Swann Karl 
Published: April 2021

ABSTRACT
Fusion of sperm and egg plasma membranes is an early and essential event at fertilization but it is not known if it plays a part in the signal transduction mechanism that leads to the oscillations in the cytoplasmic free Ca2+ concentration ([Ca2+]i) that accompany mammalian egg activation. We have used two independent fluorescence methods and confocal microscopy to show that cytoplasmic continuity of egg and sperm precedes the onset of the first [Ca2+]i increase in mouse eggs. The Ca2+ indicator dye Ca2+-green dextran was microinjected and its transfer from egg to sperm was monitored. We found that it occurred before, and without a requirement for, any detectable [Ca2+]i increase in the egg. In separate experiments [Ca2+]i changes were recorded in populations of eggs, using fura red, and the eggs fixed at various times after some of the eggs had shown a [Ca2+]i transient. Fusion of the sperm and egg was then assessed by Hoechst dye transfer. All eggs that showed a [Ca2+]i increase had a fused sperm but more than half of the eggs contained a sperm but had not undergone a [Ca2+]i increase. These data indicate that sperm-egg fusion precedes [Ca2+]i changes and we estimate that the elapsed time between sperm-egg fusion and the onset of the [Ca2+]i oscillations is 1-3 minutes. Finally, sperm-egg fusion was prevented by using low pH medium which reversibly prevented [Ca2+]i oscillations in eggs that had been inseminated. This was not due to disruption of signalling mechanisms, since [Ca2+]i changes still occurred if low pH was applied after the onset of oscillations at fertilization. [Ca2+]i changes also occurred in eggs in low pH in response to the muscarinic agonist carbachol. These data are consistent with the idea that the [Ca2+]i signals that occur in mammalian eggs at fertilization are initated by events that are closely coupled to the fusion of the sperm and egg membranes.