bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis
Authors: Kreidberg Jordan A. , Donovan Michael J. , Goldstein Stuart L. , Rennke Helmut , Shepherd Kenneth , Jones Rosemary C. , Jaenisch Rudolf 
Published: April 2021

ABSTRACT
A mutation was targeted to the murine α3 integrin gene. Homozygous mutant mice survived to birth, but died during the neonatal period. The mutation caused abnormal kidney and lung development. Mutant kidneys displayed decreased branching of the medullary collecting ducts, although the number of nephrons was not altered. Proximal tubules exhibited two distinct subsets of abnormalities, with the epithelial cells either containing excess lysosomes or becoming microcystic. In addition, glomerular development was markedly affected. In mutant kidneys, the extent of branching of glomerular capillary loops was decreased, with capillary lumina being wider than normal. The glomerular basement membrane was disorganized and glomerular podocytes were unable to form mature foot processes. Branching of the bronchi in lungs of mutant mice was also decreased and the large bronchi extended to the periphery. These results indicate a role for integrin receptors in basement membrane organization and branching morphogenesis.
Failure of ventral body wall closure in mouse embryos lacking a procollagen C-proteinase encoded by Bmp1, a mammalian gene related to Drosophila tolloid
Authors: Suzuki Noboru , Labosky Patricia A. , Furuta Yasuhide , Hargett Linda , Dunn Ray , Fogo Agnes B. , Takahara Kazuhiko , Peters Donna M. P. , Greenspan Daniel S. , Hogan Brigid L. M. 
Published: April 2021

ABSTRACT
The mouse bone morphogenetic protein1 (Bmp1) gene encodes a secreted astacin metalloprotease that cleaves the COOH-propeptide of procollagen I, II and III. BMP-1 is also related to the product of the Drosophila patterning gene, tolloid (tld), which enhances the activity of the TGFβ-related growth factor Decapentaplegic and promotes deveopment of the dorsalmost amnioserosa. We have disrupted the mouse Bmp1 gene by deleting DNA sequences encoding the active site of the astacin-like protease domain common to all splice variants. Homozygous mutant embryos appear to have a normal skeleton, apart from reduced ossification of certain skull bones. However, they have a persistent herniation of the gut in the umbilical region and do not survive beyond birth. Analysis of the amnion of homozygous mutant embryos reveals the absence of the fold that normally tightly encloses the physiological hernia of the gut. At the electron microscopic level, the extracellular matrix of the amnion contains collagen fibrils with an abnormal morphology, consistent with the incorporation of partially processed procollagen molecules. Metabolical labelling and immunofluorescence studies also reveal abnormal processing and deposition of procollagen by homozygous mutant fibroblasts in culture.
Flowering as metamorphosis: two sequential signals regulate floral initiation in Lolium temulentum
Authors: McDaniel Carl N. , Hartnett Laura K. 
Published: April 2021

ABSTRACT
We investigated floral initiation in the long-day monocot Lolium temulentum, strain Ceres, by culturing apices explanted from photoperiodically induced plants at various times after one inductive long day onto medium with, and without, gibberellin. Apices cultured on the first day after the inductive long day usually required gibberellin in the medium to initiate floral morphogenesis while apices explanted on the second day after induction did not require gibberellin. Apices explanted on the first day after induction onto medium without gibberellin grew vegetatively for many days but a several-day exposure to culture medium with gibberellin at any time caused most apices to initiate floral morphogenesis. The gibberellin synthesis inhibitor, ancymidol, when applied to plants before apex excision and when present in the culture medium reduced floral initiation by more than 50% in the absence of added gibberellin in the medium, but it was ineffective in the presence of gibberellin. These results indicated that floral initiation in photoperiodically induced plants resulted from two signals acting at the apex. The first signal induced the apex into a florally determined state and then the second signal, gibberellin, elicited expression of the florally determined state. Leaf removal and culture of apices from plants previously treated with gibberellin provided evidence that the leaf-applied gibberellin did not itself act on the apex to cause floral determination or initiation. Rather, the exogenous gibberellin appeared to stimulate the production of a signal in the leaves that then led to floral initiation.
Location and behavior of dorsal determinants during first cell cycle in Xenopus eggs
Authors: Kikkawa Mika , Takano Kazuhiro , Shinagawa Atsunori 
Published: April 2021

ABSTRACT
In Xenopus eggs, removal of small volumes of cytoplasm along with the surface (2-10% of the entire egg volume) causes very severe dorsal reduction (average DAI=1.4) when made at a site ventrally 30° off the vegetal pole at 20% time of first cell cycle (0.2 NT). The greatest dorsal reduction (average DAI=1.1) occurs when removal is done at the vegetal pole at 0.3 NT, and intermediate reductions (average DAI=2.2-2.6) when done at sites dorsally, dorsolaterally or laterally 30° off the vegetal pole at 0.4 NT. Removal at sites dorsally, dorsolaterally or laterally 60° off the vegetal pole provokes slight dorsal reduction (average DAI=3.5-3.9) when made at 0.4-0.5 NT. Removal at all sites after 0.4 NT causes a steady decrease in the extent of dorsal reduction. By contrast, removal of larger volumes of dorsal cytoplasm (16-50% of the entire egg volume) causes a steady increase in the extent of dorsal reduction during first cell cycle with its maximum effect at 1.0 NT (average DAI=3.1). The surgery for the cytoplasmic removal does not affect cortical rotation. We conclude from these results that dorsal determinants are concentrated first in a small region ventrally 30° off the vegetal pole by 0.2 NT, then move toward the vegetal pole during the period 0.2-0.3 NT and disperse to a broad region spanning over both the presumptive dorsal and ventral, but mainly the dorsal, hemispheres during the period 0.3-0.8 NT.
Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway
Authors: Shawber Carrie , Nofziger Donna , Hsieh James J.-D. , Lindsell Claire , Bögler Oliver , Hayward Diane , Weinmaster Gerry 
Published: April 2021

ABSTRACT
Notch controls cell fate by inhibiting cellular differentiation, presumably through activation of the transcriptional regulator human C promoter Binding Factor (CBF1), which transactivates the hairy and Enhancer of split (HES-1) gene. However, we describe constitutively active forms of Notch1, which inhibit muscle cell differentiation but do not interact with CBF1 or upregulate endogenous HES-1 expression. In addition, Jagged-Notch interactions that prevent the expression of muscle cell specific genes do not involve the upregulation of endogenous HES-1. In fact, exogenous expression of HES-1 in C2C12 myoblasts does not block myogenesis. Our data demonstrate the existence of a CBF1-independent pathway by which Notch inhibits differentiation. We therefore propose that Notch signaling activates at least two different pathways: one which involves CBF1 as an intermediate and one which does not.
Incomplete sister chromatid separation is the mechanism of programmed chromosome elimination during early Sciara coprophila embryogenesis
Authors: Phalle Brigitte de Saint , Sullivan William 
Published: April 2021

ABSTRACT
Sex in Sciara coprophila is determined by maternally supplied factors that control the number of paternal X chromosomes eliminated during the syncytial embryonic divisions. Confocal microscopy and FISH demonstrate that the centromeres of the X chromosomes separate at anaphase and remain functional during the cycle in which the X chromosomes are eliminated. However, a region of the sister chromatids fails to separate and the X chromosomes remain at the metaphase plate. This indicates that failure of sister chromatid separation is the mechanism of chromosome elimination. Elimination of the X chromosomes requires the presence of a previously discovered Controlling Element that acts in cis during male meiosis. Using an X-autosome translocation, we demonstrate that the Controlling Element acts at-a-distance to prevent sister chromatid separation in the arm of an autosome. This indicates that the region in which sister chromatid separation fails is chromosome-independent. Although chromosome elimination occurs in all somatic nuclei and is independent of location of the nuclei within the embryo, the decision to eliminate is made at the level of the individual nucleus. Programmed X chromosome elimination occurs at different cycles in male and female embryos. These observations support a model in which elements on the X chromosome are titrating maternally supplied factors controlling the separation of sister X chromatids.
Unequal cleavage in leech embryos: zygotic transcription is required for correct spindle orientation in a subset of early blastomeres
Authors: Bissen Shirley T. , Smith Constance M. 
Published: April 2021

ABSTRACT
Leech embryos undergo invariant sequences of equal and unequal cell divisions to give rise to identifiable progeny cells. While many of the early cleavages are under maternal control, the divisions of a subset of early blastomeres (the large cells of the D′ lineage) are perturbed after the inhibition of zygotic transcription. Analysis of the different types of cells produced in embryos injected with the transcriptional inhibitor, α-amanitin, revealed that the symmetry of cell division is perturbed in these large D′derived cells during this early period of development. These cells, which would normally undergo a series of equal and unequal cleavages, always undergo equal cleavages after the inhibition of zygotic transcription. It appears that zygotically transcribed gene product(s) are required in the large cells of the D′ lineage to orient the mitotic spindles properly for these unequal cell cleavages.
The Drosophila Serum Response Factor gene is required for the formation of intervein tissue of the wing and is allelic to blistered
Authors: Montagne Jacques , Groppe Jay , Guillemin Karen , Krasnow Mark A. , Gehring Walter J. , Affolter Markus 
Published: April 2021

ABSTRACT
The adult Drosophila wing is formed by an epithelial sheet, which differentiates into two non-neural tissues, vein or intervein. A large number of genes, many of them encoding components of an EGF-receptor signaling pathway, have previously been shown to be required for differentiation of vein tissue. Much less is known about the molecular control of intervein differentiation. Here we report that the Drosophila homolog of the mammalian Serum Response Factor gene (DSRF), which encodes a MADS-box containing transcriptional regulator, is expressed in the future intervein tissue of wing imaginal discs. In adult flies carrying only one functional copy of the DSRF gene, additional vein tissue develops in the wing, indicating that DSRF is required to spatially restrict the formation of veins. In mitotic clones lacking DSRF, intervein tissue fails to differentiate and becomes vein-like in appearance. Genetic and molecular evidence demonstrates that DSRF is encoded by the blistered locus, which produces ectopic veins and blistered wings when mutant. Our results show that DSRF plays a dual role during wing differentiation. It acts in a dosage-dependant manner to suppress the formation of wing veins and is required cell-autonomously to promote the development of intervein cells. We propose that DSRF acts at a key step between regulatory genes that define the early positional values in the developing wing disc and the subsequent localized expression of interveinspecific structural genes.
In vivo requirement for the paired domain and homeodomain of the paired segmentation gene product
Authors: Bertuccioli Claudio , Fasano Laurent , Jun Susie , Wang Sheng , Sheng Guojun , Desplan Claude 
Published: April 2021

ABSTRACT
The Drosophila pair-rule gene paired is required for the correct expression of the segment polarity genes wingless, engrailed and gooseberry. It encodes a protein containing three conserved motifs: a homeodomain (HD), a paired domain (PD) and a PRD (His/Pro) repeat. We use a rescue assay in which paired (or a mutated version of paired in which the functions of the conserved motifs have been altered) is expressed under the control of its own promoter, in the absence of endogenous paired, to dissect the Paired protein in vivo. We show that both the HD and the Nterminal subdomain of the PD (PAI domain) are absolutely required within the same molecule for normal paired function. In contrast, the conserved C-terminal subdomain of the PD (RED domain) appears to be dispensable. Furthermore, although a mutation abolishing the ability of the homeodomain to dimerize results in an impaired Paired molecule, this molecule is nonetheless able to mediate a high degree of rescue. Finally, a paired transgene lacking the PRD repeat is functionally impaired, but still able to rescue to viability. We conclude that, while Prd can use its DNA-binding domains combinatorially in order to achieve different DNA-binding specificities, its principal binding mode requires a cooperative interaction between the PAI domain and the homeodomain.
The regulation of Krox-20 expression reveals important steps in the control of peripheral glial cell development
Authors: Murphy Paula , Topilko Piotr , Schneider-Maunoury Sylvie , Seitanidou Tania , Evercooren Annick Baron-Van , Charnay Patrick 
Published: April 2021

ABSTRACT
The zinc finger transcription factor gene Krox-20 is expressed in Schwann cells and is required for the myelination of peripheral nerves. We show that the regulation of Krox-20 expression in peripheral glial cells reveals three important steps in the development and differentiation of these cells. (i) Expression of Krox-20 in Schwann cells requires continuous neuronal signalling via direct axonal contact. Therefore Krox-20 appears to be a key component of the transduction cascade linking axonal signalling to myelination. (ii) Krox-20 inducibility is acquired by Schwann cells at the time that they are formed from their precursors. Diffusible factor(s) synthesised by the neural tube can mediate this transition and can be mimicked by NDFβ or a combination of CNTF and bFGF. Furthermore, the neural tube activity is blocked by a hybrid protein containing the NDF-binding domain of the ErbB4 receptor, strongly implicating NDF in the physiological transition. (iii) In sensory ganglia, the microenvironment is capable of negatively regulating Krox-20, presumably by preventing the conversion of satellite glial cells toward a Schwann celllike phenotype.
Integrin-dependent adhesive activity is spatially controlled by inductive signals at gastrulation
Authors: Ramos Joe W. , Whittaker Charles A. , DeSimone Douglas W. 
Published: April 2021

ABSTRACT
Integrins mediate cell-ECM interactions essential for morphogenesis, however, the extent to which integrin adhesive activities are regulated in the embryo has not been addressed. We report that integrin-dependent cell adhesion to the Arg-Gly-Asp (RGD) containing central cell-binding domain of fibronectin is required for gastrulation in Xenopus. Although all cells of the early embryo retain the ability to attach to this region, only involuting cells arising from the dorsal and ventral lips of the blastopore are able to spread and migrate on fibronectin in vitro. This change in adhesive behavior is mimicked by treating animal cap cells with activin-A. Activin-induced changes in adhesion are independent of new transcription, translation, or changes in receptor expression at the cell surface. We demonstrate that ectopic expression of integrin α4β1 in animal cap cells results in attachment to the non RGD-containing V-region of fibronectin. Further, these cells acquire the ability to spread on the V-region following activin induction. Thus, α4β1 adhesion to the V-region, like endogenous integrin binding to the central cell-binding domain, is responsive to activin signalling. These data indicate that cell adhesion to the central cell-binding domain is regulated in both space and time, and is under the control of inductive signals that initiate gastrulation movements. We suggest that position-specific inductive interactions are likely to represent a novel and general mechanism by which integrin adhesion is modulated throughout development.
Mice homozygous for an insertional mutation in the Zp3 gene lack a zona pellucida and are infertile
Authors: Rankin Tracy , Familari Mary , Lee Eric , Ginsberg Ann , Dwyer Nancy , Blanchette-Mackie Joan , Drago John , Westphal Heiner , Dean Jurrien 
Published: April 2021

ABSTRACT
Mammalian oocytes synthesize and secrete a zona pellucida that surrounds the growing oocytes, ovulated eggs and preimplantation embryos. The extracellular zona matrix is composed of three glycoproteins (ZP1, ZP2, ZP3) that are involved in folliculogenesis, species-specific fertilization, and passage of the early embryo down the oviduct. We have established a mouse line in which Zp3 has been inactivated by homologous recombination with an insertional mutation. Neither Zp3 transcripts nor ZP3 protein was detected in female mice homozygous for the mutation (Zp3−/−), whereas both ZP1 and ZP2 were present in mutant oocytes. Homozygous mutant Zp3−/− mice had follicles with germinal-vesicle-intact oocytes but that lacked a zona pellucida matrix and had a disorganized corona radiata. Although mutant oocytes underwent germinal vesicle breakdown (GVBD) prior to ovulation, the cumulus-oocyte complex was markedly disrupted and the oocytes were often separate from the cumulus cells. After hormone-induced ovulation, cumulus masses were present in the oviducts of homozygous mutant mice, but zona-free eggs were observed in only half of the females and, in these, less than 10% of the normal mumber of eggs were detected. No zona-free 2-cell embryos were recovered from homozygous mutant Zp3−/− female mice after mating with males proven to be fertile, and none became visibly pregnant or produced offspring. These results demonstrate that a genetic defect in a zona pellucida gene causes infertility and, given the conserved nature of the zona pellucida, a similar phenotype is expected in other mammals.
Association of Engrailed homeoproteins with vesicles presenting caveolae-like properties
Authors: Joliot Alain , Trembleau Alain , Raposo Graça , Calvet Sophie , Volovitch Michel , Prochiantz Alain 
Published: April 2021

ABSTRACT
We report here that the homeoproteins Engrailed-1 and Engrailed-2 are present in specific non-nuclear subcellular compartments. Using electron microscopy, we observed that chick-Engrailed-2 expressed in COS-7 cells associates with membrane fractions that are characterized as caveolae. This characterization is based on morphological, biochemical and immunological criteria such as, in particular, the absence of clathrin coat and the presence of caveolin and cholera toxin-binding sites. These data are fully confirmed by subcellular fractionation experiments, which demonstrate that transfected chick-Engrailed-2 is present in low density membrane fractions that are resistant to Triton X-100, enriched in caveolin and solubilized by the addition of a cholesterol-binding detergent, a set of properties highly characteristic of caveolae. The association of Engrailed-2 with specific membrane fractions observed after transfection in COS-7 cells is also observed for endogenous Engrailed-1 and Engrailed-2 expressed at late embryonic stages in the cerebellum and posterior mesencephalon of the rodent. Indeed, the two proteins are present in membrane fractions that bear all the characteristics of microdomains or caveolae-like domains, i.e. Triton X-100 resistance, saponin solubilization, low density on sucrose gradients, enrichment in glycosphingolipid GM1, absence of transmembrane Neural Cell Adhesion Molecule, presence of the glypiated (GPI-anchored) glycoprotein F3/F11 and of the acylated growth-associated protein GAP-43. Finally we demonstrate that part of the membrane-associated Engrailed, either expressed in COS-7 cells or endogenously present in neural tissues, is not accessible to proteolytic enzymes unless the membranes have been permeabilized with detergent. This study suggests that, in addition to their well-known presence in the nucleus, Engrailed proteins are also associated with caveolae-like vesicles that are primarily transported anterogradely into the axon, and that they can get access to a compartment compatible with secretion.
Notch signalling regulates veinlet expression and establishes boundaries between veins and interveins in the Drosophila wing
Authors: Celis Jose F. de , Bray Sarah , Garcia-Bellido Antonio 
Published: April 2021

ABSTRACT
The veins in the Drosophila wing have a characteristic width, which is regulated by the activity of the Notch pathway. The expression of the Notch-ligand Delta is restricted to the developing veins, and coincides with places where Notch transcription is lower. We find that this asymmetrical distribution of ligand and receptor leads to activation of Notch on both sides of each vein within a territory of Delta-expressing cells, and to the establishment of boundary cells that separate the vein from adjacent interveins. In these cells, the expression of the Enhancer of split gene m β is activated and the transcription of the veinpromoting gene veinlet is repressed, thus restricting vein differentiation. We propose that the establishment of vein thickness utilises a combination of mechanisms that include: (1) independent regulation of Notch and Delta expression in intervein and vein territories, (2) Notch activation by Delta in cells where Notch and Delta expression overlaps, (3) positive feedback on Notch transcription in cells where Notch has been activated and (4) repression of veinlet transcription by E(spl)m β and maintenance of Delta expression by veinlet/torpedo activity.
Competition and cooperation among receptor tyrosine phosphatases control motoneuron growth cone guidance in Drosophila
Authors: Desai Chand J. , Krueger Neil X. , Saito Haruo , Zinn Kai 
Published: April 2021

ABSTRACT
The neural receptor tyrosine phosphatases DPTP69D, DPTP99A and DLAR are involved in motor axon guidance in the Drosophila embryo. Here we analyze the requirements for these three phosphatases in growth cone guidance decisions along the ISN and SNb motor pathways. Any one of the three suffices for the progression of ISN pioneer growth cones beyond their first intermediate target in the dorsal muscle field. DLAR or DPTP69D can facilitate outgrowth beyond a second intermediate target, and DLAR is uniquely required for formation of a normal terminal arbor. A different pattern of partial redundancy among the three phosphatases is observed for the SNb pathway. Any one of the three suffices to allow SNb axons to leave the common ISN pathway at the exit junction. When DLAR is not expressed, however, SNb axons sometimes bypass their ventrolateral muscle targets after leaving the common pathway, instead growing out as a separate bundle adjacent to the ISN. This abnormal guidance decision can be completely suppressed by also removing DPTP99A, suggesting that DLAR turns off or counteracts a DPTP99A signal that favors the bypass axon trajectory. Our results show that the relationships among the tyrosine phosphatases are complex and dependent on cellular context. At growth cone choice points along one nerve, two phosphatases cooperate, while along another nerve these same phosphatases can act in opposition to one another.