bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel cell-cell interactions during vulva development in Pristionchus pacificus
Authors: Jungblut Benno , Sommer Ralf J. 
Published: April 2021

ABSTRACT
Vulva development differs between Caenorhabditis elegans and Pristionchus pacificus in several ways. Seven of 12 ventral epidermal cells in P. pacificus die of apoptosis, whereas homologous cells in C. elegans fuse with the hypodermal syncytium. Vulva induction is a one-step process in C. elegans, but requires a continuous interaction between the gonad and the epidermis in P. pacificus. Here we describe several novel cell-cell interactions in P. pacificus, focusing on the vulva precursor cell P8.p and the mesoblast M. P8.p in P. pacificus, unlike its homologous cell in C. elegans, is incompetent to respond to gonadal signaling in the absence of other vulva precursor cells, but can respond to lateral signaling from a neighboring vulval precursor. P8.p provides an inhibitory signal that determines the developmental competence of P(5,7).p. This lateral inhibition acts via the mesoblast M and is regulated by the homeotic gene Ppa-mab-5. In Ppa-mab-5 mutants, M is misspecified and provides inductive signaling to the vulval precursor cells, including P8.p. Taken together, vulva development in P. pacificus displays novel cell-cell interactions involving the mesoblast M and P8.p. In particular, P8.p represents a new ventral epidermal cell type, which is characterized by novel interactions and a specific response to gonadal signaling.
Axis-inducing activities and cell fates of the zebrafish organizer
Authors: Saúde Leonor , Woolley Katie , Martin Paul , Driever Wolfgang , Stemple Derek L. 
Published: April 2021

ABSTRACT
We have investigated axis-inducing activities and cellular fates of the zebrafish organizer using a new method of transplantation that allows the transfer of both deep and superficial organizer tissues. Previous studies have demonstrated that the zebrafish embryonic shield possesses classically defined dorsal organizer activity. When we remove the morphologically defined embryonic shield, embryos recover and are completely normal by 24 hours post-fertilization. We find that removal of the morphological shield does not remove all goosecoid- and floating head-expressing cells, suggesting that the morphological shield does not comprise the entire organizer region. Complete removal of the embryonic shield and adjacent marginal tissue, however, leads to a loss of both prechordal plate and notochord. In addition, these embryos are cyclopean, show a significant loss of floor plate and primary motorneurons and display disrupted somite patterning. Motivated by apparent discrepancies in the literature we sought to test the axis-inducing activity of the embryonic shield. A previous study suggested that the shield is capable of only partial axis induction, specifically being unable to induce the most anterior neural tissues. Contrary to this study, we find shields can induce complete secondary axes when transplanted into host ventral germ-ring. In induced secondary axes donor tissue contributes to notochord, prechordal plate and floor plate. When explanted shields are divided into deep and superficial fragments and separately transplanted we find that deep tissue is able to induce the formation of ectopic axes with heads but lacking posterior tissues. We conclude that the deep tissue included in our transplants is important for proper head formation.
Signaling and transcriptional regulation in early mammalian eye development: a link between FGF and MITF
Authors: Nguyen Minh-Thanh T. , Arnheiter Heinz 
Published: April 2021

ABSTRACT
During vertebrate eye development, the optic vesicle is partitioned into a domain at its distal tip that will give rise to the neuroretina, and another at its proximal base that will give rise to the pigmented epithelium. Both domains are initially bipotential, each capable of giving rise to either neuroretina or pigmented epithelium. The partitioning depends on extrinsic signals, notably fibroblast growth factors, which emanate from the overlying surface ectoderm and induce the adjacent neuroepithelium to assume the neuroretinal fate. Using explant cultures of mouse optic vesicles, we demonstrate that bipotentiality of the optic neuroepithelium is associated with the initial coexpression of the basic-helix-loop-helix-zipper transcription factor MITF, which is later needed solely in the pigmented epithelium, and a set of distinct transcription factors that become restricted to the neuroretina. Implantation of fibroblast growth factor-coated beads close to the base of the optic vesicle leads to a rapid downregulation of MITF and the development of an epithelium that, by morphology, gene expression, and lack of pigmentation, resembles the future neuroretina. Conversely, the removal of the surface ectoderm results in the maintenance of MITF in the distal optic epithelium, lack of expression of the neuroretinal-specific CHX10 transcription factor, and conversion of this epithelium into a pigmented monolayer. This phenomenon can be prevented by the application of fibroblast growth factor alone. In Mitf mutant embryos, parts of the future pigment epithelium become thickened, lose expression of a number of pigment epithelium transcription factors, gain expression of neuroretinal transcription factors, and eventually transdifferentiate into a laminated second retina. The results support the view that the bipotential optic neuroepithelium is characterized by overlapping gene expression patterns and that selective gene repression, brought about by local extrinsic signals, leads to the separation into discrete expression domains and, hence, to domain specification.
Functional equivalence of the transcription factors Pax2 and Pax5 in mouse development
Authors: Bouchard Maxime , Pfeffer Peter , Busslinger Meinrad 
Published: April 2021

ABSTRACTPax2 and Pax5 arose by gene duplication at the onset of vertebrate evolution and have since diverged in their developmental expression patterns. They are expressed in different organs of the mouse embryo except for their coexpression at the midbrain-hindbrain boundary (MHB), which functions as an organizing center to control midbrain and cerebellum development. During MHB development, Pax2 expression is initiated prior to Pax5 transcription, and Pax2–/– embryos fail to generate the posterior midbrain and cerebellum, whereas Pax5–/– mice exhibit only minor patterning defects in the same brain regions. To investigate whether these contrasting phenotypes are caused by differences in the temporal expression or biochemical activity of these two transcription factors, we have generated a knock-in (ki) mouse, which expresses a Pax5 minigene under the control of the Pax2 locus. Midbrain and cerebellum development was entirely rescued in Pax25ki/5ki embryos. Pax5 could furthermore completely substitute for the Pax2 function during morphogenesis of the inner ear and genital tracts, despite the fact that the Pax5 transcript of the Pax25ki allele was expressed only at a fivefold lower level than the wild-type Pax2 mRNA. As a consequence, the Pax25ki allele was able to rescue most but not all Pax2 mutant defects in the developing eye and kidney, both of which are known to be highly sensitive to Pax2 protein dosage. Together these data demonstrate that the transcription factors Pax2 and Pax5 have maintained equivalent biochemical functions since their divergence early in vertebrate evolution.
Reconciling different models of forebrain induction and patterning: a dual role for the hypoblast
Authors: Foley, Ann C. , Skromne Isaac , Stern Claudio D. 
Published: April 2021

ABSTRACTSeveral models have been proposed for the generation of the rostral nervous system. Among them, Nieuwkoop’s activation/transformation hypothesis and Spemann’s idea of separate head and trunk/tail organizers have been particularly favoured recently. In the mouse, the finding that the visceral endoderm (VE) is required for forebrain development has been interpreted as support for the latter model. Here we argue that the chick hypoblast is equivalent to the mouse VE, based on fate, expression of molecular markers and characteristic anterior movements around the time of gastrulation. We show that the hypoblast does not fit the criteria for a head organizer because it does not induce neural tissue from naÏve epiblast, nor can it change the regional identity of neural tissue. However, the hypoblast does induce transient expression of the early markers Sox3 and Otx2. The spreading of the hypoblast also directs cell movements in the adjacent epiblast, such that the prospective forebrain is kept at a distance from the organizer at the tip of the primitive streak. We propose that this movement is important to protect the forebrain from the caudalizing influence of the organizer. This dual role of the hypoblast is more consistent with the Nieuwkoop model than with the notion of separate organizers, and accommodates the available data from mouse and other vertebrates.Movies available on-line: http://www.biologists.com/Development/movies/dev4408.html
A phospholipid kinase regulates actin organization and intercellular bridge formation during germline cytokinesis
Authors: Brill Julie A. , Hime Gary R. , Scharer-Schuksz Manuela , Fuller Margaret T. 
Published: April 2021

ABSTRACT
The endgame of cytokinesis can follow one of two pathways depending on developmental context: resolution into separate cells or formation of a stable intercellular bridge. Here we show that the four wheel drive (fwd) gene of Drosophila melanogaster is required for intercellular bridge formation during cytokinesis in male meiosis. In fwd mutant males, contractile rings form and constrict in dividing spermatocytes, but cleavage furrows are unstable and daughter cells fuse together, producing multinucleate spermatids. fwd is shown to encode a phosphatidylinositol 4-kinase (PI 4-kinase), a member of a family of proteins that perform the first step in the synthesis of the key regulatory membrane phospholipid PIP2. Wild-type activity of the fwd PI 4-kinase is required for tyrosine phosphorylation in the cleavage furrow and for normal organization of actin filaments in the constricting contractile ring. Our results suggest a critical role for PI 4-kinases and phosphatidylinositol derivatives during the final stages of cytokinesis.
Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo
Authors: Dick Alexander , Hild Marc , Bauer Hermann , Imai Yoshiyuki , Maifeld Heike , Schier Alexander F. , Talbot William S. , Bouwmeester Tewis , Hammerschmidt Matthias 
Published: April 2021

ABSTRACT
Bone morphogenetic proteins (Bmps) are signaling molecules that have been implicated in a variety of inductive processes. We report here that zebrafish Bmp7 is disrupted in snailhouse (snh) mutants. The allele snhst1 is a translocation deleting the bmp7 gene, while snhty68 displays a Val→Gly exhange in a conserved motif of the Bmp7 prodomain. The snhty68 mutation is temperature-sensitive, leading to severalfold reduced activity of mutant Bmp7 at 28°C and non-detectable activity at 33°C. This prodomain lesion affects secretion and/or stability of secreted mature Bmp7 after processing has occurred. Both snhst1 and snhty68 mutant zebrafish embryos are strongly dorsalized, indicating that bmp7 is required for the specification of ventral cell fates during early dorsoventral patterning. At higher temperature, the phenotype of snhty68 mutant embryos is identical to that caused by the amorphic bmp2b mutation swirl swrta72 and similar to that caused by the smad5 mutation somitabun sbndtc24 . mRNA injection studies and double mutant analyses indicate that Bmp2b and Bmp7 closely cooperate and that Bmp2b/Bmp7 signaling is transduced by Smad5 and antagonized by Chordino.
Developmental role of the SNF1-related kinase Hunk in pregnancy-induced changes in the mammary gland
Authors: Gardner Heather Perry , Belka George K. , Wertheim Gerald B. W. , Hartman Jennifer L. , Ha Seung I. , Gimotty Phyllis A. , Marquis Sandra T. , Chodosh Lewis A. 
Published: April 2021

ABSTRACT
The steroid hormones 17β;-estradiol and progesterone play a central role in the pathogenesis of breast cancer and regulate key phases of mammary gland development. This suggests that developmental regulatory molecules whose activity is influenced by ovarian hormones may also contribute to mammary carcinogenesis. In a screen designed to identify protein kinases expressed in the mammary gland, we previously identified a novel SNF1-related serine/threonine kinase, Hunk (hormonally upregulated Neu-associated kinase). During postnatal mammary development, Hunk mRNA expression is restricted to a subset of mammary epithelial cells and is temporally regulated with highest levels of expression occurring during early pregnancy. In addition, treatment of mice with 17β;-estradiol and progesterone results in the rapid and synergistic upregulation of Hunk expression in a subset of mammary epithelial cells, suggesting that the expression of this kinase may be regulated by ovarian hormones. Consistent with the tightly regulated pattern of Hunk expression during pregnancy, mammary glands from transgenic mice engineered to misexpress Hunk in the mammary epithelium manifest temporally distinct defects in epithelial proliferation and differentiation during pregnancy, and fail to undergo normal lobuloalveolar development. Together, these observations suggest that Hunk may contribute to changes in the mammary gland that occur during pregnancy in response to ovarian hormones.
Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick
Authors: Fuhrmann Sabine , Levine Edward M. , Reh Thomas A. 
Published: April 2021

ABSTRACT
The vertebrate eye develops from the neuroepithelium of the ventral forebrain by the evagination and formation of the optic vesicle. Classical embryological studies have shown that the surrounding extraocular tissues – the surface ectoderm and extraocular mesenchyme – are necessary for normal eye growth and differentiation. We have used explant cultures of chick optic vesicles to study the regulation of retinal pigmented epithelium (RPE) patterning and differentiation during early eye development. Our results show that extraocular mesenchyme is required for the induction and maintenance of expression of the RPE-specific genes Mitf and Wnt13 and the melanosomal matrix protein MMP115. In the absence of extraocular tissues, RPE development did not occur. Replacement of the extraocular mesenchyme with cranial mesenchyme, but not lateral plate mesoderm, could rescue expression of the RPE-marker Mitf. In addition to activating expression of RPE-specific genes, the extraocular mesenchyme inhibits the expression of the neural retina-specific transcription factor Chx10 and downregulates the eye-specific transcription factors Pax6 and Optx2. The TGFβ family member activin can substitute for the extraocular mesenchyme by promoting expression of the RPE-specific genes and downregulating expression of the neural retina-specific markers. These data indicate that extraocular mesenchyme, and possibly an activin-like signal, pattern the domains of the optic vesicle into RPE and neural retina.
Tissue-specific regulation ofcyclin Etranscription duringDrosophila melanogasterembryogenesis
Authors: Jones Lynn , Richardson Helena , Saint Robert 
Published: April 2021

ABSTRACTCyclin E is an essential regulator of S phase entry. We have previously shown that transcriptional regulation of the gene that encodes Drosophila cyclin E, DmcycE, plays an important role in the control of the G1 to S phase transition during development. We report here the first comprehensive analysis of the transcriptional regulation of a G1 phase cell cycle regulatory gene during embryogenesis. Analysis of deficiencies, a genomic transformant and reporter gene constructs revealed that DmcycE transcription is controlled by a large and complex cis-regulatory region containing tissue-and stage-specific components. Separate regulatory elements for transcription in epidermal cells during cell cycles 14-16, central nervous system cells and peripheral nervous system cells were found. An additional cis-regulatory element drives transcription in thoracic epidermal cells that undergo a 17th cell cycle when other epidermal cells have arrested in G1 phase prior to terminal differentiation. The complexity of DmcycE transcriptional regulation argues against a model in which DmcycE transcription is regulated simply and solely by G1 to S phase transcription regulators such as RB, E2F and DP. Rather, our study demonstrates that tissue-specific transcriptional regulatory mechanisms are important components of the control of cyclin E transcription and thus of cell proliferation in metazoans.
Establishment of left/right asymmetry in neuroblast migration by UNC-40/DCC, UNC-73/Trio and DPY-19 proteins in C. elegans
Authors: Honigberg Lee , Kenyon Cynthia 
Published: April 2021

ABSTRACT
The bilateral C. elegans neuroblasts QL and QR are born in the same anterior/posterior (A/P) position, but polarize and migrate left/right asymmetrically: QL migrates toward the posterior and QR migrates toward the anterior. After their migrations, QL but not QR switches on the Hox gene mab-5. We find that the UNC-40/netrin receptor and a novel transmembrane protein DPY-19 are required to orient these cells correctly. In unc-40 or dpy-19 mutants, the Q cells polarize randomly; in fact, an individual Q cell polarizes in multiple directions over time. In addition, either cell can express MAB-5. Both UNC-40 and DPY-19, as well as the Trio/GTPase exchange factor homolog UNC-73, are required for full polarization and migration. Thus, these proteins appear to participate in a signaling system that orients and polarizes these migrating cells in a left/right asymmetrical fashion during development. The C. elegans netrin UNC-6, which guides many cells and axons along the dorsoventral axis, is not involved in Q cell polarization, suggesting that a different netrin-like ligand serves to polarize these cells along the anteroposterior axis.
Zic3 is involved in the left-right specification of the Xenopus embryo
Authors: Kitaguchi Tetsuya , Nagai Takeharu , Nakata Katsunori , Aruga Jun , Mikoshiba Katsuhiko 
Published: April 2021

ABSTRACT
Establishment of left-right (L-R) asymmetry is fundamental to vertebrate development. Several genes involved in L-R asymmetry have been described. In the Xenopus embryo, Vg1/activin signals are implicated upstream of asymmetric nodal related 1 (Xnr1) and Pitx2 expression in L-R patterning. We report here that Zic3 carries the left-sided signal from the initial activin-like signal to determinative factors such as Pitx2. Overexpression of Zic3 on the right side of the embryo altered the orientation of heart and gut looping, concomitant with disturbed laterality of expression of Xnr1 and Pitx2, both of which are normally expressed in the left lateral plate mesoderm. The results indicate that Zic3 participates in the left-sided signaling upstream of Xnr1 and Pitx2. At early gastrula, Zic3 was expressed not only in presumptive neuroectoderm but also in mesoderm. Correspondingly, overexpression of Zic3 was effective in the L-R specification at the early gastrula stage, as revealed by a hormone-inducible Zic3 construct. The Zic3 expression in the mesoderm is induced by activin β or Vg1, which are also involved in the left-sided signal in L-R specification. These findings suggest that an activin-like signal is a potent upstream activator of Zic3 that establishes the L-R axis. Furthermore, overexpression of the zinc-finger domain of Zic3 on the right side is sufficient to disturb the L-R axis, while overexpression of the N-terminal domain on the left side affects the laterality. These results suggest that Zic3 has at least two functionally important domains that play different roles and provide a molecular basis for human heterotaxy, which is an L-R pattern anomaly caused by a mutation in human ZIC3.
FGF signalling controls the timing of Pax6 activation in the neural tube
Authors: Bertrand Nicolas , Médevielle François , Pituello Fabienne 
Published: April 2021

ABSTRACT
We have recently demonstrated that Pax6 activation occurs in phase with somitogenesis in the spinal cord. Here we show that the presomitic mesoderm exerts an inhibitory activity on Pax6 expression. This repressive effect is mediated by the FGF signalling pathway. The presomitic mesoderm displays a decreasing caudorostral gradient of FGF8, and grafting FGF8-soaked beads at the level of the neural tube abolishes Pax6 activation. Conversely, when FGF signalling is disrupted, Pax6 is prematurely activated in the neural plate. We propose that the progression of Pax6 activation in the neural tube is controlled by the caudal regression of the anterior limit of FGF activity. Hence, as part of its posteriorising activity, FGF8 downregulation acts as a switch from early (posterior) to a later (anterior) state of neural epithelial development.
Development of cranial parasympathetic ganglia requires sequential actions of GDNF and neurturin
Authors: Enomoto Hideki , Heuckeroth Robert O. , Golden Judith P. , Johnson Eugene M. , Milbrandt Jeffrey 
Published: April 2021

ABSTRACT
The neurotrophic factors that influence the development and function of the parasympathetic branch of the autonomic nervous system are obscure. Recently, neurturin has been found to provide trophic support to neurons of the cranial parasympathetic ganglion. Here we show that GDNF signaling via the RET/GFRα1 complex is crucial for the development of cranial parasympathetic ganglia including the submandibular, sphenopalatine and otic ganglia. GDNF is required early for proliferation and/or migration of the neuronal precursors for the sphenopalatine and otic ganglia. Neurturin exerts its effect later and is required for further development and maintenance of these neurons. This switch in ligand dependency during development is at least partly governed by the altered expression of GFRα receptors, as evidenced by the predominant expression of GFRα2 in these neurons after ganglion formation.
The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development
Authors: Brouns Madeleine R. , Matheson Stephen F. , Hu Kang-Quan , Delalle Ivana , Caviness Verne S. , Silver Jerry , Bronson Roderick T. , Settleman Jeffrey 
Published: April 2021

ABSTRACT
Rho GTPases direct actin rearrangements in response to a variety of extracellular signals. P190 RhoGAP (GTPase activating protein) is a potent Rho regulator that mediates integrin-dependent adhesion signaling in cultured cells. We have determined that p190 RhoGAP is specifically expressed at high levels throughout the developing nervous system. Mice lacking functional p190 RhoGAP exhibit several defects in neural development that are reminiscent of those described in mice lacking certain mediators of neural cell adhesion. The defects reflect aberrant tissue morphogenesis and include abnormalities in forebrain hemisphere fusion, ventricle shape, optic cup formation, neural tube closure, and layering of the cerebral cortex. In cells of the neural tube floor plate of p190 RhoGAP mutant mice, polymerized actin accumulates excessively, suggesting a role for p190 RhoGAP in the regulation of Rho-mediated actin assembly within the neuroepithelium. Significantly, several of the observed tissue fusion defects seen in the mutant mice are also found in mice lacking MARCKS, the major substrate of protein kinase C (PKC), and we have found that p190 RhoGAP is also a PKC substrate in vivo. Upon either direct activation of PKC or in response to integrin engagement, p190 RhoGAP is rapidly translocated to regions of membrane ruffling, where it colocalizes with polymerized actin. Together, these results suggest that upon activation of neural adhesion molecules, the action of PKC and p190 RhoGAP leads to a modulation of Rho GTPase activity to direct several actin-dependent morphogenetic processes required for normal neural development.