bluuebunny/crossref_metadata_2025_split huggingface dataset:
The active migration of Drosophila primordial germ cells
Authors: Jaglarz Mariusz K. , Howard Kenneth R. 
Published: April 2021

ABSTRACT
We describe our analysis of primordial germ cell migration in Drosophila wild-type and mutant embryos using high resolution microscopy and primary culture in vitro. During migratory events the germ cells form transient interactions with each other and surrounding somatic cells. Both in vivo and in vitro they extend pseudopodia and the accompanying changes in the cytoskeleton suggest that actin polymerization drives these movements.
These cellular events occur from the end of the blastoderm stage and are regulated by environmental cues. We show that the vital transepithelial migration allowing exit from the gut primordium and passage into the interior of the embryo is facilitated by changes in the structure of this epithelium.
Migrating germ cells extend processes in different directions. This phenomenon also occurs in primary culture where the cells move in an unoriented fashion at substratum concentration-dependent rates. In vivo this migration is oriented leading germ cells to the gonadal mesoderm. We suggest that this guidance involves stabilization of states of an intrinsic cellular oscillator resulting in cell polarization and oriented movement.
Blastomere derivation and domains of gene expression in the Spemann Organizer of Xenopus laevis
Authors: Vodicka Marie A. , Gerhart John C. 
Published: April 2021

ABSTRACT
Spemann’s Organizer, located in the dorsal marginal zone of the amphibian gastrula, induces and differentiates dorsal axial structures characteristic of this and other vertebrates. To trace the cellular origins of the Xenopus Organizer, we labelled dorsal blastomeres of three of the four tiers (A, B and C) of the 32-cell embryo with green, red and blue fluorescent lineage tracers. A strong vegetalward displacement of labelled clones occurs between the late blastula and early gastrula stages but clones mix only slightly at their borders. The typical early gastrula Organizer is composed of approximately 10% A1 progeny in its animalmost region, 70% B1 progeny in the central region, and 20% C1 progeny in vegetal and deep regions. Variability in the composition of the early gastrula Organizer results from variability in the position of early cleavage planes and in pregastrulation movements. As the Organizer involutes during gastrulation, forming dorsal axial mesoderm, clonal boundaries are greatly dispersed by cell intermixing. Within a clone, deep cells are displaced and intermixed more than superficial cells. Variability in the distribution of progeny in the dorsal axial mesoderm of the late gastrula results mostly from variable intermixing of cells during gastrulation. Experiments to perturb later developmental events by molecular or embryonic manipulations at an early stage must take this variability into account along with the majority distributions of the fate map. Within the early gastrula Organizer, the genes Xbra, goosecoid, noggin and xNR3 are expressed differently in the animal-vegetal and superficial-deep dimensions. In situ hybridization and lineage labelling define distinct regions of the dorsal marginal zone. By the end of gastrulation, dorsal axial mesoderm cells derived from the Organizer have altered their expression of the genes Xbra, goosecoid, noggin and xNR3. At a given stage, a cell’s position in the embryo rather than its lineage may be more important in determining which genes it will express.
Pattern formation in Drosophila head development: the role of the orthodenticle homeobox gene
Authors: Royet Julien , Finkelstein Robert 
Published: April 2021

ABSTRACT
Significant progress has been made towards understanding how pattern formation occurs in the imaginal discs that give rise to the limbs of Drosophila melanogaster. Here, we examine the process of regional specification that occurs in the eye-antennal discs, which form the head of the adult fruitfly. We demonstrate genetically that there is a graded requirement for the activity of the orthodenticle homeobox gene in forming specific structures of the developing head. Consistent with this result, we show that OTD protein is expressed in a graded fashion across the disc primordia of these structures and that different threshold levels of OTD are required for the formation of specific subdomains of the head. Finally, we provide evidence suggesting that otd acts through the segment polarity gene engrailed to specify medial head development.
The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates
Authors: Chow King L. , Hall David H. , Emmons Scott W. 
Published: April 2021

ABSTRACT
The gene mab-21, which encodes a novel protein of 386 amino acids, is required for the choice of alternate cell fates by several cells in the C. elegans male tail. Three cells descended from the ray 6 precursor cell adopt fates of anterior homologs, and a fourth, lineally unrelated hypodermal cell is transformed into a neuroblast. The affected cells lie together in the lateral tail epidermis, suggesting that mab-21 acts as part of a short-range pattern-formation mechanism. Each of the changes in cell fate brought about by mab-21 mutants can be interpreted as a posterior-toanterior homeotic transformation. mab-21 mutant males and hermaphrodites have additional pleiotropic phenotypes affecting movement, body shape and fecundity, indicating that mab-21 has functions outside the tail region of males. We show that the three known alleles of mab-21 are hypomorphs of a new gene. Mosaic analysis revealed that mab-21 acts cell autonomously to specify the properties of the sensory ray, but non-autonomously in the hypodermal versus neuroblast cell fate choice. Presence of cell signalling in the choice of the neuroblast fate was confirmed by cell ablation experiments. Mutations in mab-21 were shown previously to be genetic modifiers of the effects of HOMC/Hox gene mutations on ray identity specification. The results presented here support the conclusion that mab-21 acts as part of a mechanism required for correct cell fate choice, possibly involving the function of HOM-C/Hox genes in several body regions.
Target-independent diversification and target-specific projection of chemically defined retinal ganglion cell subsets
Authors: Yamagata Masahito , Sanes Joshua R. 
Published: April 2021

ABSTRACT
In diverse vertebrate species, defined subsets of retinal ganglion cells (RGCs, the neurons that project from retina to brain) are distinguishable on the basis of their dendritic morphology, physiological properties, neurotransmitter content and synaptic targets. Little is known about when this diversity arises, whether diversification requires targetderived signals, and how subtype-specific projection patterns are established. Here, we have used markers for two chemically defined RGC subsets in chick retina to address these issues. Antibodies to substance P (SP) and the nicotinic acetylcholine receptor (AChR) β2 subunit label two small (&lt;10%), mutually exclusive groups of RGCs in mature retina. SP and AChRs accumulate in distinct RGCs before retinotectal synapses have formed. Moreover, both populations of RGCs form in retinae that develop following tectal ablation or transplantation to the coelomic cavity. Thus, RGC subsets acquire distinct neurotransmitter phenotypes in the absence of extraretinal cues.
In the mature optic tectum, SPand AChR-positive RGC axonal arbors are confined to distinct retinorecipient (synaptic) laminae. In the developing tectum, Spand AChR-positive axons are initially intermingled in a superficial fiber layer, but then enter and arborize in appropriate laminae soon after those laminae form. Importantly, SPpositive axons, which synapse in a superficial lamina, never extend into the deeper, AChR-positive lamina. Tectal interneurons rich in SP receptors are concentrated in the lamina to which SP-positive RGC axons project, and a set of cholinergic (choline acetyltransferase-positive) tectal projection neurons elaborate dendrites in the lamina to which AChR-positive RGC axons project. These populations of tectal neurons, which are likely targets of the RGC subsets, form in tecta that develop following enucleation. Thus, RGCs and their targets can diversify in each others absence. Accordingly, we propose that the lamina-selective connectivity we observe reflects the presence of complementary cues on RGC subsets and their laminar targets.
Ligands of steroid/thyroid receptors induce cone photoreceptors in vertebrate retina
Authors: Kelley Matthew W. , Turner Jennifer K. , Reh Thomas A. 
Published: April 2021

ABSTRACT
The mechanisms by which multipotent progenitor cells are directed to alternative cell identities during the histogenesis of the vertebrate central nervous system are likely to involve several different types of signaling systems. Recent evidence indicates that 9-cis retinoic acid, which acts through members of the steroid/thyroid superfamily of receptors, directs progenitor cells to the rod photoreceptor cell fate. We now report that another effector of this family of receptors, thyroid hormone, induces an increase in the number of cone photoreceptors that develop in embryonic rat retinal cultures, and that combinations of 9-cis retinoic acid and triiodothyronine cause isolated progenitor cells to differentiate as either rods or cones, depending on the relative concentrations of the ligands. These results implicate thyroid hormone in CNS cell fate determination, and suggest that different photoreceptor phenotypes may be modulated through the formation of thyroid/retinoid receptor heterodimers.
The Drosophila homeotic target gene centrosomin (cnn) encodes a novel centrosomal protein with leucine zippers and maps to a genomic region required for midgut morphogenesis
Authors: Heuer Josef G. , Li Kaijun , Kaufman Thomas C. 
Published: April 2021

ABSTRACT
The products of the homeotic genes in Drosophila are transcription factors that are necessary to impose regional identity along the anterior-posterior axis of the developing embryo. However, the target genes under homeotic regulation that control this developmental process are largely unknown. We have utilized an immunopurification method to clone target genes of the Antennapedia protein (ANTP). We present here the characterization of centrosomin (cnn), one of the target genes isolated using this approach. The spatial and temporal expression of the cnn gene in the developing visceral mesoderm (VM) of the midgut and the central nervous system (CNS) of wild-type and homeotic mutant embryos is consistent with the idea that cnn is a homeotic target. In the VM, Antp and abdominal-A (abd-A) negatively regulate cnn, while Ultrabithorax (Ubx) shows positive regulation. In the CNS, cnn is regulated positively by Antp and negatively by Ubx and abd-A. Characterization of a cDNA encoding CNN predicts a novel structural protein with three leucine zipper motifs and several coiledcoil domains exhibiting limited homology to the rod portion of myosin. Immunocytochemical results demonstrate that the cnn encoded protein is localized to the centrosome and the accumulation pattern is coupled to the nuclear and centrosome duplication cycles of cleavage. In addition, evidence suggests that the expression of the cnn gene in the VM correlates with the morphogenetic function of Ubx in that tissue, i.e., the formation of the second midgut constriction. The centrosomal localization of CNN and the involvement of microtubules in midgut morphogenesis suggest that this protein may participate in mitotic spindle assembly and the mechanics of morphogenesis through an interaction with microtubules, either directly or indirectly.
Longitudinal organization of the anterior neural plate and neural tube
Authors: Shimamura Kenji , Hartigan Dennis J. , Martinez Salvador , Puelles Luis , Rubenstein John L. R. 
Published: April 2021

ABSTRACT
Over the last century, several morphological models of forebrain organization have been proposed that hypothesize alternative topological solutions for the relationships of the histogenic primordia. Central to all of these models are their definitions of the longitudinal axis and the longitudinal organization of the neural plate and neural tube. To understand the longitudinal organization of the anterior brain, we have sought to identify molecular properties that are continuous along the entire longitudinal axis of the embryonic CNS. In this essay, we describe studies of the expression of several genes in the mouse between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide evidence for the trajectory of the anteriorposterior axis and the longitudinal organization of the anterior CNS.
Specifically, we report that the expression of noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are present along the entire CNS axis. Within the forebrain, the expression of these genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions in the neural plate and tube. We demonstrate that the earliest longitudinal axon pathways of the forebrain are spatially correlated with the longitudinal domain defined by Nkx-2.2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic neural plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the neural plate.
The role of yan in mediating the choice between cell division and differentiation
Authors: Rogge Ronald , Green Patricia J. , Urano Jun , Horn-Saban Shirley , Mlodzik Marek , Shilo Ben-Zion , Hartenstein Volker , Banerjee Utpal 
Published: April 2021

ABSTRACT
An allele of the yan locus was isolated as an enhancer of the Ellipse mutation of the Drosophila epidermal growth factor receptor (Egfr) gene. This yan allele is an embryonic lethal and also fails to complement the lethality of anterior open (aop) mutations. Phenotypic and complementation analysis revealed that aop is allelic to yan and genetically the lethal alleles act as null mutations for the yan gene. Analysis of the lethal alleles in the embryo and in mitotic clones showed that loss of yan function causes cells to overproliferate in the dorsal neuroectoderm of the embryo and in the developing eye disc. Our studies suggest that the role of yan is defined by the developmental context of the cells in which it functions. An important role of this gene is in allowing a cell to choose between cell division and differentiation. The relationship of the Egfr and Notch pathways to this devel- opmental role of yan is discussed.
Expression of a truncated FGF receptor results in defective lens development in transgenic mice
Authors: Robinson Michael L. , MacMillan-Crow L. A. , Thompson John A. , Overbeek Paul A. 
Published: April 2021

ABSTRACT
Members of the fibroblast growth factor (FGF) family are thought to initiate biological responses through the activation of cell surface receptors which must dimerize to transmit an intracellular signal. Mammalian lens epithelial cells respond to exogenous extracellular FGF, either in tissue culture or in transgenic mice, by initiating fiber cell differentiation. The role of FGF signalling in normal lens development was evaluated by lens-specific synthesis of a kinase-deficient FGF receptor type I (FGFR1) in transgenic mice. This truncated FGF receptor is thought to act as a dominant negative protein by heterodimerization with endogenous FGF receptors. The presence of transgenic mRNA in the lens was confirmed by in situ hybridization and by polymerase chain reaction amplification of reverse transcribed lens RNA (RT-PCR). The presence of transgenic protein was determined by Western blotting with antibodies to an extracellular domain of FGFR1. Three of four transgenic families expressing the truncated FGF receptor exhibited lens defects ranging from cataracts to severe microphthalmia. While the microphthalmic lenses displayed a normal pattern of differentiation-specific crystallin expression, the lens epithelial cells were reduced in number and the lens fiber cells displayed characteristics consistent with the induction of apoptosis. Our results support the view that FGF receptor signalling plays an essential role in normal lens biology.
Evolution of neuroblast identity: seven-up and prospero expression reveal homologous and divergent neuroblast fates in Drosophila and Schistocerca
Authors: Broadus Julie , Doe Chris Q. 
Published: April 2021

ABSTRACT
In the Drosophila CNS, early neuroblast formation and fate are controlled by the pair-rule class of segmentation genes. The distantly related Schistocerca (grasshopper) embryo has a similar arrangement of neuroblasts, despite lack of known pair-rule gene function. Does divergent pair-rule gene function lead to different neuroblast identities, or can different patterning mechanisms produce homologous neuroblasts? We use four molecular markers to compare Drosophila and Schistocerca neuroblast identity: seven-up, prospero, engrailed, and fushi-tarazu/Dax. In both insects some early-forming neuroblasts share key features of neuroblast identity (position, time of formation, and temporally accurate gene expression); thus, different patterning mechanisms can generate similar neuroblast fates. In contrast, several later-forming neuroblasts show speciesspecific differences in position and/or gene expression; these neuroblast identities seem to have diverged, suggesting that evolution of the insect central nervous system can occur through changes in embryonic neuroblast identity.
Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain
Authors: Xu Qiling , Alldus Graham , Holder Nigel , Wilkinson David G. 
Published: April 2021

ABSTRACT
During development of the vertebrate hindbrain regulatory gene expression is confined to precise segmental domains. Studies of cell lineage and gene expression suggest that establishment of these domains may involve a dynamic regulation of cell identity and restriction of cell movement between segments. We have taken a dominant negative approach to interfere with the function of Sek-1, a member of the Eph-related receptor tyrosine kinase family expressed in rhombomeres r3 and r5. In Xenopus and zebrafish embryos expressing truncated Sek-1, lacking kinase sequences, expression of r3/r5 markers occurs in adjacent even-numbered rhombomeres, in domains contiguous with r3 or r5. This disruption is rescued by fulllength Sek-1, indicating a requirement for the kinase domain in the segmental restriction of gene expression. These data suggest that Sek-1, perhaps with other Ephrelated receptors, is required for interactions that regulate the segmental identity or movement of cells.
The gene virilizer is required for female-specific splicing controlled by Sxl, the master gene for sexual development in Drosophila
Authors: Hilfiker Andres , Amrein Hubert , Dübendorfer Andreas , Schneiter Roger , Nöthiger Rolf 
Published: April 2021

ABSTRACT
The gene virilizer (vir) is needed for dosage compensation and sex determination in females and for an unknown vital function in both sexes. In genetic mosaics, XX somatic cells mutant for vir differentiate male structures. One allele, vir2f, is lethal for XX, but not for XY animals. This femalespecific lethality can be rescued by constitutive expression of Sxl or by mutations in msl (male-specific lethal) genes. Rescued animals develop as strongly masculinized intersexes or pseudomales. They have male-specifically spliced mRNA of tra, and when rescued by msl, also of Sxl. Our data indicate that vir is a positive regulator of femalespecific splicing of Sxl and of tra pre-mRNA.
Evolutionary conservation of a cell fate specification gene: the Hydra achaete-scute homolog has proneural activity in Drosophila
Authors: Grens Ann , Mason Elizabeth , Marsh J. Lawrence , Bode Hans R. 
Published: April 2021

ABSTRACT
Members of the Achaete-scute family of basic helix-loophelix transcription factors are involved in cell fate specification in vertebrates and invertebrates. We have isolated and characterized a cnidarian achaete-scute homolog, CnASH, from Hydra vulgaris, a representative of an evolutionarily ancient branch of metazoans. There is a single achaete-scute gene in Hydra, and the bHLH domain of the predicted gene product shares a high degree of amino acid sequence similarity with those of vertebrate and Drosophila Achaete-scute proteins. In Hydra, CnASH is expressed in a subset of the interstitial cells as well as differentiation intermediates of the nematocyte pathways. In vitro translated CnASH protein can form heterodimers with the Drosophila bHLH protein Daughterless, and these dimers bind to consensus Achaete-scute DNA binding sites in a sequence-specific manner. Ectopic expression of CnASH in wild-type late third instar Drosophila larvae and early pupae leads to the formation of ectopic sensory organs, mimicking the effect of ectopic expression of the endogenous achaete-scute genes. Expression of CnASH in flies that are achaete and scute double mutants gives partial rescue of the mutant phenotype, comparable to the degree of rescue obtained by ectopic expression of the Drosophila genes. These results indicate that the achaete-scute type of bHLH genes for cell fate specification, as well as their mode of action, arose early and have been conserved during metazoan evolution.
Pax-2 controls multiple steps of urogenital development
Authors: Torres Miguel , Gómez-Pardo Emilia , Dressler Gregory R. , Gruss Peter 
Published: April 2021

ABSTRACT
Urogenital system development in mammals requires the coordinated differentiation of two distinct tissues, the ductal epithelium and the nephrogenic mesenchyme, both derived from the intermediate mesoderm of the early embryo. The former give rise to the genital tracts, ureters and kidney collecting duct system, whereas mesenchymal components undergo epithelial transformation to form nephrons in both the mesonephric (embryonic) and metanephric (definitive) kidney. Pax-2 is a transcriptional regulator of the paired-box family and is widely expressed during the development of both ductal and mesenchymal components of the urogenital system. We report here that Pax-2 homozygous mutant newborn mice lack kidneys, ureters and genital tracts. We attribute these defects to dysgenesis of both ductal and mesenchymal components of the developing urogenital system. The Wolffian and Müllerian ducts, precursors of male and female genital tracts, respectively, develop only partially and degenerate during embryogenesis. The ureters, inducers of the metanephros are absent and therefore kidney development does not take place. Mesenchyme of the nephrogenic cord fails to undergo epithelial transformation and is not able to form tubules in the mesonephros. In addition, we show that the expression of specific markers for each of these components is de-regulated in Pax-2 mutants. These data show that Pax-2 is required for multiple steps during the differentiation of intermediate mesoderm. In addition, Pax-2 mouse mutants provide an animal model for human hereditary kidney diseases.