bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Danforth’s short tail mutation acts cell autonomously in notochord cells and ventral hindgut endoderm
Authors: Maatman Ronald , Zachgo Jochen , Gossler Achim 
Published: April 2021

ABSTRACT
Danforth’s short tail (Sd) is a semidominant mutation in mouse affecting the axial skeleton and urogenital system. The notochord is the first visibly abnormal structure in mutant embryos, and disintegrates beginning around embryonic day 9.5 along its entire length, suggesting an essential role for Sd in notochord development and main-tenance.
Here, we report on the fate of Sd/+ and Sd/Sd cells in chimeric embryos. Up to day 9-9.5, Sd cells contributed effi-ciently to the notochord of chimeric embryos. In advanced day 9.5 embryos, Sd cells were less abundant in the posterior-most region of the notochord and in the noto-chordal plate. During subsequent development, Sd cells were specifically lost from the notochord and replaced by wild-type cells. In Sd/+↔+/+ chimeras, the notochord appeared histologically and functionally normal, leading to a rescue of the mutant phenotype. However, strong Sd/Sd↔+/+ chimeras showed malformations of the axial skeleton and urogenital system. All Sd/Sd↔+/+ chimeras with malformations of the axial skeleton also had kidney defects, whereas chimeras without vertebral column defects had highly chimeric kidneys that appeared normal, suggesting that the urogenital malformations arise secon-darily to impaired posterior development caused by the degenerating notochord. Sd mutant cells also were specifi-cally absent from the ventral portion of the hindgut, whereas they contributed efficiently to the dorsal region, implying the existence of distinct cell populations in the dorsal and ventral hindgut.
Our findings demonstrate that the Sd mutation acts cell autonomously in cells of the notochord and ventral hind gut. Sd leads to the degeneration of notochord cells and the number or allocation of notochord precursors from the tail bud to the notochordal plate seems impaired, whereas notochord formation from the node appears to be unaffected.
Drosophila tissue polarity requires the cell-autonomous activity of the fuzzy gene, which encodes a novel transmembrane protein
Authors: Collier Simon , Gubb David 
Published: April 2021

ABSTRACT
The tissue polarity gene fuzzy (fy) has two roles in the devel-opment of Drosophila wing hairs. One is to specify the correct orientation of the hair by limiting the site of prehair initiation to the distal vertex of the wing cell. The other is to control wing cell hair number by maintaining the integrity of the cytoskeletal components that direct hair development. The requirement for fy in these processes is temperature dependent, as the amorphic fy phenotype is cold sensitive. Analysis of mosaic wings has shown that the fy gene product functions cell autonomously. We have cloned the fy transcript, which encodes a novel four-pass transmembrane protein that shares significant homology with proteins encoded by vertebrate cDNAs. The fourth putative transmembrane domain does not appear to play a significant role in tissue polarity as it is deleted in a weak fy hypomorph. Expression of the fy transcript is develop-mentally regulated and peaks sharply at the time of wing cell pre-hair initiation.
Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium
Authors: Sainio Kirsi , Suvanto Petro , Davies Jamie , Wartiovaara Jorma , Wartiovaara Kirmo , Saarma Mart , Arumäe Urmas , Meng Xiaojuan , Lindahl Maria , Pachnis Vassilis , Sariola Hannu 
Published: April 2021

ABSTRACT
The shapes of different organs can be explained largely by two fundamental characteristics of their epithelial rudiments – the pattern of branching and the rate of pro-liferation. Glial-cell-line-derived neurotrophic factor (GDNF) has recently been implicated in the development of metanephric ureteric epithelium (Pichel, J. G., Shen, L., Sheng, H. Z., Granholm, A.-C., Drago, J., Grinberg, A., Lee, E. J., Huang, S. P., Saarma, M., Hoffer, B.J., Sariola, H. and Westphal, H. (1996). Nature 382, 73-76; Sánchez, M.P., Silos-Santiago, I., Frisén, J., He, B., Lira, S.A. and Barbacid, M. (1996). Nature 382, 70-73; Vega, Q.C., Worby, C.A., Lechner, M.S., Dixon, J.E. and Dressler, G.R. (1996). Proc. Nat. Acad. Sci. USA 93, 10657-10661). We have analysed the target cells of GDNF and the manner in which it controls ureteric development, and have compared it with other growth factors that have been associated with the regulation of branching morphogenesis, namely hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGFβ1). We show that GDNF binds directly to the tips of ureteric bud branches, and that it has the ability to promote primary ureteric buds from various segments of Wolffian duct and to attract ureteric branches towards the source of GDNF. It increases cell adhesion, but is not obviously mitogenic for ureteric cells. The data indicate that GDNF is required primarily for bud initiation. Com-parison of GDNF, HGF and TGFβ1 suggests that the latter act later than GDNF, and may represent a partially redundant set of mesenchyme-derived growth factors that control ureteric development. Thus, GDNF is the first defined inducer in the embryonic metanephric kidney.
dally, a Drosophila glypican, controls cellular responses to the TGF-β-related morphogen, Dpp
Authors: Jackson Shari M. , Nakato Hiroshi , Sugiura Motoko , Jannuzi Alison , Oakes Robert , Kaluza Vesna , Golden Catherine , Selleck Scott B. 
Published: April 2021

ABSTRACT
Decapentaplegic (Dpp) is a Drosophila member of the Transforming Growth Factor-β (TGF-β)/Bone Morpho-genetic Protein (BMP) superfamily of growth factors. Dpp serves as a classical morphogen, where concentration gradients of this secreted factor control patterning over many cell dimensions. Regulating the level of Dpp signaling is therefore critical to its function during development. One type of molecule proposed to modulate growth factor signaling at the cell surface are integral membrane proteo-glycans. We show here that division abnormally delayed (dally), a Drosophila member of the glypican family of integral membrane proteoglycans is required for normal Dpp signaling during development, affecting cellular responses to this morphogen. Ectopic expression of dally+ can alter the patterning activity of Dpp, suggesting a role for dally+ in modulating Dpp signaling strength. These findings support a role for members of the glypican family in controlling TGF-β/BMP activity in vivo by affecting signaling at the cell surface.
Animal and vegetal pole cells of early Xenopus embryos respond differently to maternal dorsal determinants: implications for the patterning of the organiser
Authors: Darras Sébastien , Marikawa Yusuke , Elinson Richard P. , Lemaire Patrick 
Published: April 2021

ABSTRACT
The maternal dorsal determinants required for the specification of the dorsal territories of Xenopus early gastrulae are located at the vegetal pole of unfertilised eggs and are moved towards the prospective dorsal region of the fertilised egg during cortical rotation. While the molecular identity of the determinants is unknown, there are dorsal factors in the vegetal cortical cytoplasm (VCC). Here, we show that the VCC factors, when injected into animal cells activate the zygotic genes Siamoisand Xnr3, suggesting that they act along the Wnt/β-catenin pathway.
In addition, Siamoisand Xnr3 are activated at the vegetal pole of UV-irradiated embryos, indicating that these two genes are targets of the VCC factors in all embryonic cells. However, the consequences of their activation in cells that occupy different positions along the animal-vegetal axis differ. Dorsal vegetal cells of normal embryos or VCC-treated injected animal cells are able to dorsalise ventral mesoderm in conjugate experiments but UV-treated vegetal caps do not have this property. This difference is unlikely to reflect different levels of activation of FGF or activilike signal transduction pathways but may reflect the activation of different targets of Siamois. Chordin, a marker of the head and axial mesoderm, is activated by the VCC/Siamois pathway in animal cells but not in vegetal cells whereas cerberus, a marker of the anterior mesendoderm which lacks dorsalising activity, can only be activated by the VCC/Siamois pathway in vegetal cells. We propose that the regionalisation of the organiser during gastrulation proceeds from the differential interpretation along the animal-vegetal axis of the activation of the VCCβ-catenin/Siamois pathway.
Neural tube-ectoderm interactions are required for trigeminal placode formation
Authors: Stark Michael R. , Sechrist John , Bronner-Fraser Marianne , Marcelle Christophe 
Published: April 2021

ABSTRACT
Cranial sensory ganglia in vertebrates develop from the ectodermal placodes, the neural crest, or both. Although much is known about the neural crest contribution to cranial ganglia, relatively little is known about how placode cells form, invaginate and migrate to their targets. Here, we identify Pax-3 as a molecular marker for placode cells that contribute to the ophthalmic branch of the trigeminal ganglion and use it, in conjunction with DiI labeling of the surface ectoderm, to analyze some of the mechanisms underlying placode development. Pax-3 expression in the ophthalmic placode is observed as early as the 4-somite stage in a narrow band of ectoderm contiguous to the midbrain neural folds. Its expression broadens to a patch of ectoderm adjacent to the midbrain and the rostral hindbrain at the 8-to 10-somite stage. Invagination of the first Pax-3-positive cells begins at the 13-somite stage. Placodal invagination continues through the 35-somite stage, by which time condensation of the trigeminal ganglion has begun. To challenge the normal tissue interactions leading to placode formation, we ablated the cranial neural crest cells or implanted barriers between the neural tube and the ectoderm. Our results demonstrate that, although the presence of neural crest cells is not mandatory for Pax-3 expression in the forming placode, a diffusible signal from the neuroectoderm is required for induction and/or maintenance of the ophthalmic placode.
Mesodermal defects and cranial neural crest apoptosis in α5 integrin-null embryos
Authors: Goh Keow Lin , Yang Joy T. , Hynes Richard O. 
Published: April 2021

ABSTRACT
α5β1 integrin is a cell surface receptor that mediates cell-extracellular matrix adhesions by interacting with fibronectin. α5 subunit-deficient mice die early in gestation and display mesodermal defects; most notably, embryos have a truncated posterior and fail to produce posterior somites. In this study, we report on the in vivo effects of the α5-null mutation on cell proliferation and survival, and on mesodermal development. We found no significant differences in the numbers of apoptotic cells or in cell proliferation in the mesoderm of α5-null embryos compared to wild-type controls. These results suggest that changes in overall cell death or cell proliferation rates are unlikely to be responsible for the mesodermal deficits seen in theα5-null embryos. No increases in cell death were seen inα5-null embryonic yolk sac, amnion and allantois compared with wild-type, indicating that the mutant phenotype is not due to changes in apoptosis rates in these extraembryonic tissues. Increased numbers of dying cells were, however, seen in migrating cranial neural crest cells of the hyoid arch and in endodermal cells surrounding the omphalomesenteric artery in α5-null embryos, indicating that these sub-populations of cells are dependent on α5 integrin function for their survival. Mesodermal markers mox-1, Notch-1, Brachyury (T) and Sonic hedgehog (Shh)were expressed in the mutant embryos in a regionally appropriate fashion. Both T and Shh, however, showed discontinuous expression in the notochords of α5-null embryos due to (1) degeneration of the notochordal tissue structure, and (2) non-maintenance of gene expression. Consistent with the disorganization of notochordal signals in the α5-null embryos, reduced Pax-1 expression and misexpression of Pax-3 were observed. Anteriorly expressed HoxB genes were expressed normally in the α5-null embryos. However, expression of the posteriormost HoxB gene, Hoxb-9, was reduced in α5-null embryos. These results suggest that α5β1-fibronectin interactions are not essential for the initial commitment of mesodermal cells, but are crucial for maintenance of meso-dermal derivatives during postgastrulation stages and also for the survival of some neural crest cells.
Forced expression of the homeodomain protein Gax inhibits cardiomyocyte proliferation and perturbs heart morphogenesis
Authors: Fisher Steven A. , Siwik Ernest , Branellec Didier , Walsh Kenneth , Watanabe Michiko 
Published: April 2021

ABSTRACT
The development of the tubular heart into a complex four-chambered organ requires precise temporal and region-specific regulation of cell proliferation, migration, death and differentiation. While the regulatory mechanisms in heart morphogenesis are not well understood, increasing attention has focused on the homeodomain proteins, which are generally linked to morphogenetic processes. The homeodomain containing gene Gax has been shown to be expressed in heart and smooth muscle tissues. In this study, the Gax protein was detected in the nuclei of myocardial cells relatively late in chicken heart development, at a time when myocyte proliferation is declining. To test the hypothesis that the Gax protein functions as a negative regulator of cardiomyocyte proliferation, a replication-defective adenovirus was used to force its precocious nuclear expression during chicken heart morphogenesis. In experiments in which Gax- and β-galactosidase-expressing adenoviruses were co-injected, clonal expansion of myocytes was reduced, consistent with inhibition of myocyte proliferation. This effect on proliferation was corroborated by the finding that the percentage of exogenous Gax-expressing myocytes that were positive for the cell cycle marker PCNA decreased over time and was lower than in control myocytes. The precocious nuclear expression of Gax in tubular hearts resulted in abnormal heart morphology, including small ventricles with rounded apices, a thinned compact zone and coarse trabeculae. These results suggest a role for the Gax protein in heart morphogenesis causing proliferating cardiomyocytes to withdraw from the cell cycle, thus influencing the size and shape that the heart ultimately attains.
The metalloprotease-disintegrin Kuzbanian participates in Notch activation during growth and patterning of Drosophila imaginal discs
Authors: Sotillos Sol , Roch Fernando , Campuzano Sonsoles 
Published: April 2021

ABSTRACT
The Notch transmembrane protein is the receptor of an evolutionary conserved pathway that mediates intercellular signalling leading to the specification of different cell types during development. In this pathway, many aspects of the signal transduction mechanism remain poorly understood, especially the role of proteolytic processing of Notch. We present genetic evidence indicating that the met-alloprotease-disintegrin kuzbanian (J. Rooke, D. Pan, T. Xu and G. M. Rubin (1996) Science 273, 1227–1231) is a new component of the Notch signalling pathway and is involved in Notch activation. kuzbanian genetic mosaics demonstrate that, during neurogenesis, wing margin formation and vein width specification kuzbanian is autonomously required in the cell where Notch is activated. Genetic interactions between kuzbanian and different genes of the Notch pathway indicate that kuzbanian is required upstream of Suppressor of Hairless. Moreover, the requirement of kuzbanian for signalling by a ligand-dependent Abruptex receptor, but not by a constitutively activated form of Notch, suggests that kuzbanian is involved in the generation of a Notch functional receptor and/or in its activation. However, differences in the phenotypes of loss-of-function Notch and kuzbanian mutations suggest the existence of alternative Kuzbanian-independent mechanisms that generate Notch functional receptors.
Gene dosage-dependent effects of the Hoxa-13 and Hoxd-13 mutations on morphogenesis of the terminal parts of the digestive and urogenital tracts
Authors: Warot Xavier , Fromental-Ramain Catherine , Fraulob Valérie , Chambon Pierre , Dollé Pascal 
Published: April 2021

ABSTRACT
Gene targeting experiments have shown that the murine Hoxa-13 and Hoxd-13 paralogous genes control skeletal patterning in the distal region of the developing limbs. However, both genes are also expressed in the terminal part of the digestive and urogenital tracts during embryogenesis and postnatal development. Here, we report the abnormalities occuring in these systems in Hoxa-13−/− and Hoxa-13/Hoxd-13 compound mutant mice. Hoxa-13−/− mutant fetuses show agenesis of the caudal portion of the Müllerian ducts, lack of development of the presumptive urinary bladder and premature stenosis of the umbilical arteries, which could account for the lethality of this mutation at mid-gestational stages. Due to such lethality, only Hoxa-13+/−/Hoxd-13−/− compound mutants can reach adulthood. These compound mutants display: (i) agenesis or hypoplasia of some of the male accessory sex glands, (ii) malpositioning of the vaginal, urethral and anal openings, and improper separation of the vagina from the urogenital sinus, (iii) hydronephrosis and (iv) anomalies of the muscular and epithelial layers of the rectum. Thus, Hoxa-13 and Hoxd-13 play important roles in the morphogenesis of the terminal part of the gut and urogenital tract. While Hoxa-13−/−/Hoxd-13+/− fetuses show severely impaired development of the urogenital sinus, double null (Hoxa-13−/−/Hoxd-13−/−) fetuses display no separation of the terminal (cloacal) hindgut cavity into a urogenital sinus and presumptive rectum, and no development of the genital bud, thereby demonstrating that both genes act, in a partly redundant manner, during early morphogenesis of posterior trunk structures.
The Bearded box, a novel 3′ UTR sequence motif, mediates negative post-transcriptional regulation of Bearded and Enhancer of split Complex gene expression
Authors: Lai Eric C. , Posakony James W. 
Published: April 2021

ABSTRACT
During the development of the Drosophila adult peripheral nervous system (PNS), inhibitory cell-cell interactions mediated by the Notch receptor are essential for proper specification of sensory organ cell fates. We have reported previously (M. W. Leviten, E. C. Lai and J. W. Posakony (1997) Development 124, 4039-4051) that the 3′ untranslated regions (UTRs) of many genes involved in Notch signalling, including Bearded (Brd) and the genes of the Enhancer of split Complex (E(spl)-C), contain (often in multiple copies) two novel heptanucleotide sequence motifs, the Brd box (AGCTTTA) and the GY box (GTCTTCC). Moreover, the molecular lesion associated with a strong gain-of-function mutant of Brd suggested that the loss of these sequence elements from its 3′ UTR might be responsible for the hyperactivity of the mutant gene. We show here that the wild-type Brd 3′ UTR confers negative regulatory activity on heterologous transcripts in vivo and that this activity requires its three Brd box elements and, to a lesser extent, its GY box. We find that Brd box-mediated regulation decreases both transcript and protein levels, and our results suggest that deadenylation or inhibition of polyadenylation is a component of this regulation. Though Brd and the E(spl)-C genes are expressed in spatially restricted patterns in both embryos and imaginal discs, we find that the regulatory activity that functions through the Brd box is both temporally and spatially general. A Brd genomic DNA transgene with specific mutations in its Brd and GY boxes exhibits hypermorphic activity that results in characteristic defects in PNS development, demonstrating that Brd is normally regulated by these motifs. Finally, we show that Brd boxes and GY boxes in the E(spl)m4 gene are specifically conserved between two distantly related Drosophila species, strongly suggesting that E(spl)-C genes are regulated by these elements as well.
Fibroblast Growth Factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung
Authors: Bellusci Savério , Grindley Justin , Emoto Hisayo , Itoh Nobuyuki , Hogan Brigid L. M. 
Published: April 2021

ABSTRACT
During mouse lung morphogenesis, the distal mesenchyme regulates the growth and branching of adjacent endoderm. We report here that fibroblast growth factor 10 (Fgf10) is expressed dynamically in the mesenchyme adjacent to the distal buds from the earliest stages of lung development. The temporal and spatial pattern of gene expression suggests that Fgf10 plays a role in directional outgrowth and possibly induction of epithelial buds, and that positive and negative regulators of Fgf10 are produced by the endoderm. In transgenic lungs overexpressing Shh in the endoderm, Fgf10 transcription is reduced, suggesting that high levels of SHH downregulate Fgf10.
Addition of FGF10 to embryonic day 11.5 lung tissue (endoderm plus mesenchyme) in Matrigel or collagen gel culture elicits a cyst-like expansion of the endoderm after 24 hours. In Matrigel, but not collagen, this is followed by extensive budding after 48-60 hours. This response involves an increase in the rate of endodermal cell proliferation. The activity of FGF1, FGF7 and FGF10 was also tested directly on isolated endoderm in Matrigel culture. Under these conditions, FGF1 elicits immediate endodermal budding, while FGF7 and FGF10 initially induce expansion of the endoderm. However, within 24 hours, samples treated with FGF10 give rise to multiple buds, while FGF7-treated endoderm never progresses to bud formation, at all concentrations of factor tested. Although exogenous FGF1, FGF7 and FGF10 have overlapping activities in vitro, their in vivo expression patterns are quite distinct in relation to early branching events. We conclude that, during early lung development, localized sources of FGF10 in the mesoderm regulate endoderm proliferation and bud outgrowth.