bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary changes of developmental mechanisms in the absence of cell lineage alterations during vulva formation in the Diplogastridae (Nematoda)
Authors: Sommer Ralf J. 
Published: April 2021

ABSTRACT
The origin of novelty is one of the least understood evolutionary phenomena. One approach to study evolutionary novelty comes from developmental biology. During developmental cell fate specification of the nematode Pristionchus pacificus (Diplogastridae), five cell fates can be distinguished within a group of twelve ventral epidermal cells. The differentiation pattern of individual cells includes programmed cell death, cell fusion and vulval differentiation after induction by the gonad. A cell lineage comparison among species of seven different genera of the Diplogastridae indicates that the differentiation pattern of ventral epidermal cells is highly conserved. Despite this morpho-logical conservation, cell ablation experiments indicate many independent alterations of underlying mechanisms of cell fate specification. Cell fusion and individual cell competence change during evolution as well as the differentiation property in response to inductive signaling. These results suggest that developmental mechanisms, some of which are redundantly involved in vulval fate specification of the genetic model organism Caenorhabditis elegans, can evolve without concomitant morphological change.
Two nested gonadal inductions of the vulva in nematodes
Authors: Félix Marie-Anne , Sternberg Paul W. 
Published: April 2021

ABSTRACT
How do intercellular signals that pattern cell fates vary in evolution? During nematode vulva development, precursor cells acquire one of three fates in a pattern centered around the gonadal anchor cell. Non-vulval fates are at the periphery, outer and inner vulval fates are towards the center. In Caenorhabditis elegans, the three fates are specified around the same time by an induction by the anchor cell and lateral signaling between the vulva precursor cells. We find that, in three other nematode species (Panagrolaimus, Oscheius and Rhabditella spp.) spanning two families, the centered pattern is obtained by two temporally distinct gonadal inductions. The first induction specifies vulval fates; the second induction specifies the inner vulval fates in a subset of the precursors’ daughters. This evolutionary change in the spatiotemporal connectivity of cell interactions allows centering of the pattern between two precursors in Panagrolaimus.
Organization and cell differentiation in lateral roots of Arabidopsis thaliana
Authors: Malamy Jocelyn E. , Benfey Philip N. 
Published: April 2021

ABSTRACT
Lateral root formation in plants involves the stimulation of mature pericycle cells to proliferate and redifferentiate to create a new organ. The simple organization of the root of Arabidopsis thaliana allows the development of lateral root primordia to be characterized histologically. We have divided the process of lateral root development into 8 stages defined by specific anatomical characteristics and cell divisions. To identify the cell types in the developing primordium we have generated a collection of marker lines that express β-glucuronidase in a tissue- or cell type-specific manner in the root. Using these tools we have constructed a model describing the lineage of each cell type in the lateral root. These studies show that organization and cell differentiation in the lateral root primordia precede the appearance of a lateral root meristem, with differential gene expression apparent after the first set of divisions of the pericycle.
Long-range genomic rearrangements upstream of Kit dysregulate the developmental pattern of Kit expression in W
57 and W
banded mice and interfere with distinct steps in melanocyte development
Authors: Klüppel Michael , Nagle Deborah L. , Bucan Maja , Bernstein Alan 
Published: April 2021

ABSTRACT
Mutations in the murine dominant white spotting (W) locus cause pleiotropic developmental defects that affect hematopoietic cells, melanocytes, germ cells and the interstitial cells of Cajal in the gut. W mutations either alter the coding sequence of the Kit receptor tyrosine kinase, resulting in a receptor with impaired kinase activity, or affect Kit expression. Here we describe the molecular and cell-type-specific developmental defects of two of the latter class of regulatory W alleles, W57 and Wbanded(bd). In both mutants, the temporal and spatial patterns of Kit expression are dysregulated during embryogenesis and in adult animals. In Wbd mice, ectopic expression of Kit in the dermatome of the somites at days 10.8 and 11.8 of development seemed to interfere with melanoblast development. In contrast, the W57 allele leads to an intrinsic pigmentation defect by downregulating developmental Kit expression in trunk melanoblasts, but not melanoblasts around the otic vesicle. Both mutations affect transcriptional initiation of the Kit gene. The W57 allele is associated with a 80 kb deletion 5′ of the Kit-coding region while Wbd is associated with a 2.8 Mb genomic inversion of chromosome 5 with the distal breakpoint between Kit and the platelet-derived growth factor receptor alpha (Pdgfra) gene, and the proximal breakpoint between the genes for the GABA receptor beta 1 (Gabrb1) and the Tec tyrosine kinase, juxtaposing the Kit and Tec tyrosine kinase genes. Neither W57 nor Wbd affect genomic sequences previously suggested in in vitro experiments to control cell-type-specific expression of Kit. These results link specific mechanisms of cellular and developmental defects to long-range genomic rearrangements that positively and negatively affect Kit transcription in different cell lineages as well as in different subpopulations of the same lineage.
Fashioning the vertebrate heart: earliest embryonic decisions
Authors: Fishman Mark C. , Chien Kenneth R. 
Published: April 2021

ABSTRACT
Our goal here is to set out the types of unitary decisions made by heart progenitor cells, from their appearance in the heart field until they form the simple heart tube. This provides a context to evaluate cell fate, lineage and, finally, morphogenetic decisions that configure global heart form and function. Some paradigms for cellular differentiation and for pattern generation may be borrowed from invertebrates, but neither Drosophila nor Caenorhabditis elegans suffice to unravel higher order decisions. Genetic analyses in mouse and zebrafish may provide one entrance to these pathways.
Analysis of competence and of Brachyury autoinduction by use of hormoneinducible Xbra
Authors: Tada M. , O’Reilly M.-A. J. , Smith J. C. 
Published: April 2021

ABSTRACT
Analysis of gene function in Xenopus development frequently involves over-expression experiments, in which RNA encoding the protein of interest is microinjected into the early embryo. By taking advantage of the fate map of Xenopus, it is possible to direct expression of the protein to particular regions of the embryo, but it has not been possible to exert control over the timing of expression; the protein is translated immediately after injection. To overcome this problem in our analysis of the role of Brachyury in Xenopus development, we have, like Kolm and Sive (1995; Dev. Biol. 171, 267-272), explored the use of hormone-inducible constructs. Animal pole regions derived from embryos expressing a fusion protein (Xbra-GR) in which the Xbra open reading frame is fused to the ligandbinding domain of the human glucocorticoid receptor develop as atypical epidermis, presumably because Xbra is sequestered by the heat-shock apparatus of the cell. Addition of dexamethasone, which binds to the glucocorticoid receptor and releases Xbra, causes formation of mesoderm. We have used this approach to investigate the competence of animal pole explants to respond to Xbra-GR, and have found that competence persists until late gastrula stages, even though by this time animal caps have lost the ability to respond to mesoderm-inducing factors such as activin and FGF. In a second series of experiments, we demonstrate that Xbra is capable of inducing its own expression, but that this auto-induction requires intercellular signals and FGF signalling. Finally, we suggest that the use of inducible constructs may assist in the search for target genes of Brachyury.
Zfx mutation results in small animal size and reduced germ cell number in male and female mice
Authors: Luoh Shiuh-Wen , Bain Paul A. , Polakiewicz Roberto D. , Goodheart Mary L. , Gardner Humphrey , Jaenisch Rudolf , Page David C. 
Published: April 2021

ABSTRACT
The zinc-finger proteins ZFX and ZFY, encoded by genes on the mammalian X and Y chromosomes, have been spec-ulated to function in sex differentiation, spermatogenesis, and Turner syndrome. We derived Zfx mutant mice by targeted mutagenesis. Mutant mice (both males and females) were smaller, less viable, and had fewer germ cells than wild-type mice, features also found in human females with an XO karyotype (Turner syndrome). Mutant XY animals were fully masculinized, with testes and male genitalia, and were fertile, but sperm counts were reduced by one half. Homozygous mutant XX animals were fully feminized, with ovaries and female genitalia, but showed a shortage of oocytes resulting in diminished fertility and shortened reproductive lifespan, as in premature ovarian failure in humans. The number of primordial germ cells was reduced in both XX and XY mutant animals at embryonic day 11.5, prior to gonadal sex differentiation. Zfx mutant animals exhibited a growth deficit evident at embryonic day 12.5, which persisted throughout postnatal life and was not complemented by the Zfy genes. These phe-notypes provide the first direct evidence for a role ofZfx in growth and reproductive development.
Hedgehog is an indirect regulator of morphogenetic furrow progression in the Drosophila eye disc
Authors: Strutt David I. , Mlodzik Marek 
Published: April 2021

ABSTRACT
Pattern formation in the eye imaginal disc of Drosophila occurs in a wave that moves from posterior to anterior. The anterior edge of this wave is marked by a contracted band of cells known as the morphogenetic furrow, behind which photoreceptors differentiate. The movement of the furrow is dependent upon the secretion of the signalling protein Hedgehog (Hh) by more posterior cells, and it has been suggested that Hh acts as an inductive signal to induce cells to enter a furrow fate and begin differentiation. To further define the rôle of Hh in this process, we have analysed clones of cells lacking the function of the smoothened (smo) gene, which is required for transduction of the Hh signal and allows the investigation of the autonomous requirement for hh signalling. These experiments demonstrate that the function of hh in furrow progression is indirect. Cells that cannot receive/transduce the Hh signal are still capable of entering a furrow fate and differentiating normally. However, hh is required to promote furrow progression and regulate its rate of movement across the disc, since the furrow is significantly delayed in smo clones.
ventral veinless, a POU domain transcription factor, regulates different transduction pathways required for tracheal branching in Drosophila
Authors: Llimargas Marta , Casanova Jordi 
Published: April 2021

ABSTRACT
Cell migration is an important step in a variety of developmental processes in many multicellular organisms. A particularly appropriate model to address the study of cell migration is the tracheal system of Drosophila, whose formation occurs by migration and fusion from clusters of ectodermal cells specified in each side of ten embryonic segments. Morphogenesis of the tracheal tree requires the activity of many genes, among them breathless (btl) and ventral veinless (vvl) whose mutations abolish tracheal cell migration. Activation of the btl receptor by branchless (bnl), its putative ligand, exerts an instructive role in the process of guiding tracheal cell migration. vvl has been shown to be required for the maintenance of btl expression during tracheal tree formation. Here we show that, in addition, vvl is independently required for the specific expression in the tracheal cells of thick veins (tkv) and rhomboid (rho), two genes whose mutations disrupt only particular branches of the tracheal system. Indeed, we show that expression in the tracheal cells of an activated form of tkv, the putative decapentaplegic (dpp) receptor, is able to induce shifts in their migration, asserting the role of the dpp pathway in establishing the branching pattern of the tracheal tree. In addition, by ubiquitous expression of the btl and tkv genes in vvl mutant embryos we show that both genes contribute to vvl function. These results indicate that through activation of its target genes, vvl makes the tracheal cells competent to further signalling and suggest that the btl transduction pathway could collaborate with other transduction pathways also regulated by vvl to specify the tracheal branching pattern.
Homeotic genes and the regulation of myoblast migration, fusion, and fibre-specific gene expression during adult myogenesis in Drosophila
Authors: Roy Sudipto , VijayRaghavan K. 
Published: April 2021

ABSTRACT
We have investigated the roles of homeotic selector genes in the migration and fusion of myoblasts, and in the differentiation of adult muscle fibres of Drosophila. Altering intrinsic homeotic identities of myoblasts does not affect their segment-specific migration patterns. By transplanting meso – and metathoracic myoblasts into the abdomen, we demonstrate that the fusion abilities of myoblasts are independent of their segmental identities. However, trans-planted thoracic myoblast nuclei are ‘entrained’ by those of the host abdominal muscles to which they fuse and are unable to ‘switch on’ a thoracic muscle-specific reporter gene. This process is likely to be mediated by homeotic repression because mis-expression of an abdominal muscle-specific homeotic gene, Ultrabithorax, in the thoracic muscles results in the repression of the thoracic muscle-specific reporter gene. Finally, we show that removal of Ultrabithorax function specifically from muscle cells of the first abdominal segment, results in the expression of thoracic muscle properties. Many of these functions of homeotic genes in muscle patterning in Drosophila could be conserved during myogenesis in other organisms.
A dominant-negative form of Serrate acts as a general antagonist of Notch activation
Authors: Hukriede Neil A. , Gu Yi , Fleming Robert J. 
Published: April 2021

ABSTRACT
Specification of the dorsal-ventral compartment boundary in the developing Drosophila wing disc requires activation of NOTCH from its dorsal ligand SERRATE and its ventral ligand DELTA. Both NOTCH ligands are required in this process and one cannot be substituted for the other. In the wing disc, expression of a dominant-negative, truncated form of SERRATE called BDG, is capable of inhibiting NOTCH activation in the ventral but not the dorsal compartments. We demonstrate that BDG can act as a general antagonist of both SERRATE and DELTA mediated NOTCH interactions, however, BDG retains the SERRATE protein domain targeted by FRINGE, hence its antagonistic effects are restricted in the dorsal wing disc. Our findings suggest a model in which ligand binding to NOTCH is a necessary but insufficient step toward NOTCH activation.
Sequential expression and role of Hu RNA-binding proteins during neurogenesis
Authors: Wakamatsu Yoshio , Weston James A. 
Published: April 2021

ABSTRACT
We have identified three avian (chicken) Hu/elav family RNA-binding protein genes. cHuD and cHuC are expressed specifically in neurons of both the central and peripheral nervous systems. Although cHuA is expressed in a wide variety of tissues, including neurogenic precursor cells, it is transiently down-regulated, and is then re-expressed in maturing neurons. Misexpression of cHuD in cultured neural crest cells results in a dramatic increase in the proportion of cells exhibiting neuronal morphology, molecular markers for neurons, and neurotrophin dependence. These data confirm that cHuD protein is involved in regulating neuronal differentiation.
Nitric oxide, an endogenous regulator of Dictyostelium discoideum differentiation
Authors: Tao Y. P. , Misko T. P. , Howlett A. C. , Klein C. 
Published: April 2021

ABSTRACT
We have previously demonstrated that nitric oxide (NO)- generating compounds inhibit D. discoideum differentiation by preventing the initiation of cAMP pulses (Tao, Y., Howlett, A. and Klein, C. (1996) Cell. Signal. 8, 37-43). In the present study, we demonstrate that cells produce NO at a relatively constant rate during the initial phase of their developmental cycle. The addition of oxyhemoglobin, an NO scavenger, stimulates cell aggregation, suggesting that NO has a negative effect on the development of aggregation competence. Starvation of cells in the presence of glucose, which has been shown to prevent the initiation of cAMP pulses (Darmon, M. and Klein, C. (1978) Dev. Biol. 63, 377-389), results in an increased production of NO. The inhibition of cell aggregation by glucose treatment can be reversed by oxyhemoglobin. These findings indicate that NO is a signaling molecule for D. discoideum cells and that physiological or environmental conditions that enhance external NO levels will delay the initiation of cAMP pulses, which are essential for cell differentiation.
Argos and Spitz group genes function to regulate midline glial cell number in Drosophila embryos
Authors: Stemerdink Christopher , Jacobs J. Roger 
Published: April 2021

ABSTRACT
The midline glia of the Drosophila embryonic nerve cord undergo a reduction in cell number after facilitating com-missural tract morphogenesis. The numbers of midline glia entering apoptosis at this stage can be increased by a loss or reduction of function in genes of the spitz group or Drosophila EGF receptor (DER) pathway. Argos, a secreted molecule with an atypical EGF motif, is postulated to function as a DER antagonist. In this work, we assess the role of argos in the determination of midline glia cell number. Although all midline glia express DER, argos expression is restricted to the midline glia which do not enter apoptosis. Fewer midline glia enter apoptosis in embryos lacking argos function. Ectopic expression of argos is sufficient to remove all DER-expressing midline glia from the nerve cord, even those that already express argos. DER expression is not terminated in the midline glia after spitz group signaling triggers changes in gene expression. It is therefore likely that an attenuation of DER signaling by Argos is integrated with the augmentation of DER signaling by Spitz throughout the period of reduction of midline glia number. We suggest that signaling by Spitz but not Argos is restricted to adhesive junctions. In this manner, midline glia not forming signaling junctions remain sensitive to juxtacrine Argos signaling, while an autocrine Argos signal is excluded by the adhesive junction.
An activity-dependent network of interactions links the Rel protein Dorsal with its cytoplasmic regulators
Authors: Edwards David N. , Towb Par , Wasserman Steven A. 
Published: April 2021

ABSTRACT
A signaling pathway active on the ventral side of the Drosophila embryo defines dorsoventral polarity. A cell surface signal relayed by Toll, Tube and Pelle releases the Rel-related protein Dorsal from its cytoplasmic inhibitor Cactus; free Dorsal translocates into nuclei and directs expression of ventral fates. Using the yeast two-hybrid system and immunoprecipitation experiments, we define scaffolding and anchoring interactions among the pathway components. We show that Dorsal binds specifically to Tube, Pelle and Cactus, and that the protein kinase activity of Pelle differentially regulates its interactions with Dorsal and Tube. We also identify Drosophila Filamin as a potential adaptor linking the interaction network, via Tube, to the transmembrane receptor Toll.
Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo
Authors: Queenan Anne Marie , Ghabrial Amin , Schüpbach Trudi 
Published: April 2021

ABSTRACT
The Drosophila gene torpedo/Egfr (top/Egfr) encodes a homolog of the vertebrate Epidermal Growth Factor receptor. This receptor is required several times during the life cycle of the fly for the transmission of developmental cues. During oogenesis, Top/Egfr activation is required for the establishment of the dorsal/ventral axis of the egg and the embryo. To examine how ectopic Top/Egfr activation affects cell fate determination, we constructed an activated version of the protein. Expression of this activated form (λtop) in the follicle cells of the ovary induces dorsal cell fates in both the follicular epithelium and the embryo. Different levels of expression resulted in different dorsal follicle cell fates. These dorsal cell fates were expanded in the anterior, but not the posterior, of the egg, even in cases where all the follicle cells covering the oocyte expressed λtop. The expression of genes known to respond to top/Egfr activation, argos (aos), kekkon1 (kek 1) and rhomboid (rho), was also expanded in the presence of the λtop construct. When λtop was expressed in all the follicle cells covering the oocyte, kek 1 and argos expression was induced in follicle cells all along the anterior/posterior axis of the egg chamber. In contrast, rho RNA expression was only activated in the anterior of the egg chamber. These data indicate that the response to Top/Egfr signaling is regulated by an anterior/posterior prepattern in the follicle cells.
Expression of λtop in the entire follicular epithelium resulted in an embryo dorsalized along the entire anterior/posterior axis. Expression of λtop in anterior or posterior subpopulations of follicle cells resulted in regionally autonomous dorsalization of the embryos. This result indicates that subpopulations of follicle cells along the anterior/posterior axis can respond to Top/Egfr activation independently of one another.
Integrins mediate adhesion to agrin and modulate agrin signaling
Authors: Martin Paul T. , Sanes Joshua R. 
Published: April 2021

ABSTRACT
Agrin, a basal lamina-associated proteoglycan, is a crucial nerve-derived organizer of postsynaptic differentiation at the skeletal neuromuscular junction. Because integrins serve as cellular receptors for many basal lamina components, we asked whether agrin interacts with integrins. Agrin-induced aggregation of acetylcholine receptors on cultured myotubes was completely blocked by antibodies to the β1 integrin subunit and partially blocked by antibodies to the αv integrin subunit. Agrin-induced clustering was also inhibited by antisense oligonucleotides to αv and a peptide that blocks the αv binding site. Non-muscle cells that expressed αv and β1 integrin subunits adhered to immobilized agrin, and this adhesion was blocked by anti-αv and anti-β1 antibodies. Integrin αv-negative cells that did not adhere to agrin were rendered adherent by introduction of αv. Together, these results implicate integrins, including αvβ1, as components or modulators of agrin’s signal transduction pathway.