bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial steps of myogenesis in somites are independent of influence from axial structures
Authors: Bober Eva , Brand-Saberi Beate , Ebensperger Cecilia , Wilting Jörg , Balling Rudi , Paterson Bruce M. , Arnold Hans-Henning , Christ Bodo 
Published: April 2021

ABSTRACT
Formation of paraxial muscles in vertebrate embryos depends upon interactions between early somites and the neural tube and notochord. Removal of both axial struc-tures results in a complete loss of epaxial myotomal muscle, whereas hypaxial and limb muscles develop normally.
We report that chicken embryos, after surgical removal of the neural tube at the level of the unsegmented paraxial mesoderm, start to develop myotomal cells that express transcripts for the muscle-specific regulators MyoD and myogenin. These cells also make desmin, indicating that the initial steps of axial skeletal muscle formation can occur in the absence of the neural tube. However, a few days following the extirpation, the expression of MyoD and myogenin transcripts gradually disappears, and becomes almost undetectable after 4 days. From these observations we conclude that the neural tube is not required for the generation of the skeletal muscle cell lineage, but may support the survival or maitenance of further differen-tiation of the myotomal cell compartment.
Notochord transplanted medially or laterally to the unsegmented paraxial mesoderm leads to a ventralization of axial structures but does not entirely prevent the early appearance of myoblasts expressing MyoD transcripts. However, the additional notochord inhibits subsequent development and maturation of myotomes. Taken together, our data suggest that neural tube promotes, and notochord inhibits, the process of myogenesis in axial muscles at a developmental step following the initial expression of myogenic bHLH regulators.
Transcriptional regulation of string (cdc25): a link between developmental programming and the cell cycle
Authors: Edgar Bruce A. , Lehman Dara A. , O’Farrell Patrick H. 
Published: April 2021

ABSTRACT
During postblastoderm embryogenesis in Drosophila, cell cycles progress in an invariant spatiotemporal pattern. Most of these cycles are differentially timed by bursts of transcription of string (cdc25), a gene encoding a phosphatase that triggers mitosis by activating the Cdc2 kinase. An analysis of string expression in 36 pattern-formation mutants shows that known patterning genes act locally to influence string transcription. Embryonic expression of string gene fragments shows that the complete pattern of string transcription requires extensive cis-acting regulatory sequences (&gt;15.3 kb), but that smaller segments of this regulatory region can drive proper temporal expression in defined spatial domains. We infer that string upstream sequences integrate many local signals to direct string’s transcriptional program. Finally, we show that the spatiotemporal progression of string transcription is largely unaffected in mutant embryos specifically arrested in G2 of cycles 14, 15, or 16, or G1 of cycle 17. Thus, there is a regulatory hierarchy in which developmental inputs, not cell cycle inputs, control the timing of string transcription and hence cell cycle progression.
Immortalizing oncogenes subvert the establishment of granule cell identity in developing cerebellum
Authors: Gao Wei-Qiang , Hatten Mary E. 
Published: April 2021

ABSTRACT
After implantation into the external germinal layer of early postnatal cerebellum, primary external germinal layer progenitor cells gave rise exclusively to granule neurons. In contrast, all major classes of cerebellar cells were observed following implantation of embryonic day 13 cerebellar precursor cells into the external germinal layer. These results suggest that granule cells arise from precursors with a restricted potential. In contrast to results with the primary external germinal layer population, cell lines established from external germinal layer cells, by infection with a retrovirus containing the SV40 large T-antigen oncogene, gave rise to several cerebellar cell types upon implantation. These included granule neurons, one subclass of stellate interneurons, Golgi cells, Bergmann glia and astrocytes. From these results, we conclude that early postnatal external germinal layer progenitors are normally fated to a granule cell identity and that expression of the SV40 large T-antigen oncogene subverts mechanisms that control granule neuron fate.
Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation
Authors: Das Sanjoy K. , Wang Xiao-Ning , Paria Bibhash C. , Damm Deborah , Abraham Judith A. , Klagsbrun Michael , Andrews Glen K. , Dey Sudhansu K. 
Published: April 2021

ABSTRACT
Heparin-binding EGF-like growth factor (HB-EGF) is a newly discovered member of the EGF family of growth factors. HB-EGF can bind to two loci on cell surfaces, heparan sulphate proteoglycans and EGF-receptor (EGFR), and either one or both of these interactions could play a role in cell-cell interactions. In the rodent, increased endometrial vascular permeability at the site of blastocyst apposition is considered to be an earliest discernible prerequisite event in the process of implantation and this event coincides with the initial attachment reaction between the blastocyst trophectoderm and uterine luminal epithelium. This investigation demonstrates that the HB-EGF gene is expressed in the mouse uterine luminal epithelium surrounding the blastocyst 6-7 hours before the attachment reaction that occurs at 2200-2300 hours on day 4 of pregnancy. It was further demonstrated that this gene is not expressed in the luminal epithelium at the site of the blastocyst apposition during the progesterone-maintained delayed implantation, but is readily induced in the luminal epithelium surrounding an activated blastocyst after termination of the delay by an estrogen injection. In vitro studies showed that HB-EGF induced blastocyst EGF-R autophosphorylation, and promoted blastocyst growth, zona-hatching and trophoblast outgrowth. These results suggest possible interactions between the uterine HB-EGF and blastocyst EGF-R very early in the process of implantation, earlier than any other embryo-uterine interactions defined to date at the molecular level.
Neurogenic and proneural genes control cell fate specification in the Drosophila endoderm
Authors: Tepass Ulrich , Hartenstein Volker 
Published: April 2021

ABSTRACT
The Drosophila endoderm segregates into three non-neural cell types, the principle midgut epithelial cells, the adult midgut precursors, and the interstitial cell precursors, early in development. We show that this process occurs in the absence of mesoderm and requires proneural and neurogenic genes. In neurogenic mutants the principle midgut epithelial cells are missing and the other two cell types develop in great excess. Consequently, the midgut epithelium does not form. In achaete-scute complex and daughterless mutants the interstitial cell precursors do not develop and the number of adult midgut precursors is strongly reduced. Development of the principle midgut epithelial cells and formation of the midgut epithelium is restored in neurogenic proneural double mutants. The neu rogenic/proneural genes are, in contrast to the neuroectoderm, not expressed in small clusters of cells but initially homogeneously in the endoderm suggesting that no prepattern exists which determines the position of the segregating cells. Hence, the segregation pattern solely depends on neurogenic/proneural gene interaction. Proneural genes are required but not sufficient to determine specific cell fates because they are required for cell type specification in both ectoderm and endoderm. Our data also suggest that the neurogenic/proneural genes are involved in the choice between epithelial versus mesenchymal cell morphologies.
Extracellular FGF-1 acts as a lens differentiation factor in transgenic mice
Authors: Robinson Michael L. , Overbeek Paul A. , Verran Deborah J. , Grizzle William E. , Stockard Cecil R. , Friesel Robert , Maciag Thomas , Thompson John A. 
Published: April 2021

ABSTRACT
The vertebrate ocular lens undergoes a spatially defined pattern of differentiation which may be regulated by the ocular distribution of proteins from the fibroblast growth factor (FGF) family. The ability of altered FGF-1 (acidic FGF) distribution to disrupt the normal pattern of lens differentiation was evaluated by the production of transgenic mice which express FGF-1 under the control of the lens-specific αA-crystallin promoter. Since FGF-1 lacks a classical signal peptide consensus sequence, transgenic mice were also produced with a chimeric construct containing the signal peptide sequence of the FGF-4 gene fused in frame to the coding sequences of the FGF-1 cDNA in order to obtain extracellular expression of the transgene. The presence of transgenic mRNA and protein was confirmed by in situ hybridization, Western analysis and immunohistochemistry. The ocular histology of newborn and young adult transgenic mice expressing FGF-1 without a signal peptide appeared normal. In contrast, mice expressing secreted FGF-1 exhibited lens abnormalities including the elongation of anterior epithelial cells. Epithelial cell elongation was accompanied by expression of the fiber cell differentiation marker, β-crystallin. These observations provide an in vivo demonstration that FGF-1 can induce anterior lens epithelial cells to express characteristics consistent with the onset of fiber cell differentiation. The transgenic induction of differentiation confirms that normal lens morphology reflects an asymmetric distribution of inductive factors within the eye.
Mutations affecting somite formation and patterning in the zebrafish, Danio rerio
Authors: van Eeden Fredericus J. M. , Granato Michael , Schach Ursula , Brand Michael , Furutani-Seiki Makoto , Haffter Pascal , Hammerschmidt Matthias , Heisenberg Carl-Philipp , Jiang Yun-Jin , Robert Donald A. Kane , Kelsh N. , Mullins Mary C. , Odenthal Jörg , Warga Rachel M. , Allende Miguel L. , Weinberg Eric S. , Nüsslein-Volhard Christiane 
Published: April 2021

ABSTRACT
Somitogenesis is the basis of segmentation of the mesoderm in the trunk and tail of vertebrate embryos. Two groups of mutants with defects in this patterning process have been isolated in our screen for zygotic mutations affecting the embryonic development of the zebrafish (Danio rerio). In mutants of the first group, boundaries between individual somites are invisible early on, although the paraxial mesoderm is present. Later, irregular boundaries between somites are present. Mutations in fused somites (fss) and beamter (bea) affect all somites, whereas mutations in deadly seven (des), after eight (aei) and white tail (wit) only affect the more posterior somites. Mutants of all genes but wit are homozygous viable and fertile. Skeletal stainings and the expression pattern of myoD and snail1 suggest that anteroposterior patterning within individual somites is abnormal. In the second group of mutants, formation of the horizontal myoseptum, which separates the dorsal and ventral part of the myotome, is reduced. Six genes have been defined in this group (you-type genes). you-too mutants show the most severe phenotype; in these the adaxial cells, muscle pioneers and the primary motoneurons are affected, in addition to the horizontal myoseptum.
The horizontal myoseptum is also missing in mutants that lack a notochord. The similarity of the somite phenotype in mutants lacking the notochord and in the you- type mutants suggests that the genes mutated in these two groups are involved in a signaling pathway from the notochord, important for patterning of the somites.
Neural degeneration mutants in the zebrafish, Danio rerio
Authors: Furutani-Seiki Makoto , Jiang Yun-Jin , Brand Michael , Heisenberg Carl-Philipp , Houart Corinne , Beuchle Dirk , Eeden Fredericus J. M. van , Granato Michael , Haffter Pascal , Hammerschmidt Matthias , Kane Donald A. , Kelsh Robert N. , Mullins Mary C. , Odenthal Jörg , Nüsslein-Volhard Christiane 
Published: April 2021

ABSTRACT
Forty zebrafish mutants with localized or general neural degeneration are described. The onset and duration of degeneration and the distribution of ectopically dying cells are specific characteristics of each mutant. Mutants are classified into four groups by these parameters. Class I: late focal neural degeneration mutants. These 18 mutants have restricted cell death mainly in the tectum and the dorsal hindbrain after 36 hours. The degeneration does not spread and disappears at later stages of development. Class II: early focal neural degeneration mutants. Ten mutants in this class exhibit transient restricted degeneration affecting mainly the diencephalon, the hindbrain and the spinal cord at 20 hours. The midbrain is less affected. The degeneration shifts to the dorsal diencephalon and the tectum at 36 hours. Class III: late spreading neural degeneration mutants. The 8 mutants in this class display a degeneration that is first seen in the tectum and subsequently spreads throughout the nervous system from 36 hours on. Class IV: early general neural degeneration mutants. This class of four mutants already shows overall cell degeneration in the nervous system at the 15-somite stage.
Three of the class I mutants show a change in the pattern of gene expression in the anlage of a brain structure prior to the onset of degeneration. These results suggest that focal cell death may be a useful clue for the detection of early patterning defects of the vertebrate nervous system in regions devoid of visible landmarks.
Spatially restricted expression of PlOtp, a Paracentrotus lividus Orthopedia- related homeobox gene, is correlated with oral ectodermal patterning and skeletal morphogenesis in late-cleavage sea urchin embryos
Authors: Di Bernardo Maria , Castagnetti Stefania , Bellomonte Daniela , Oliveri Paola , Melfi Raffaella , Palla Franco , Spinelli Giovanni 
Published: April 2021

ABSTRACT
Several homeobox genes are expressed in the sea urchin embryo but their roles in development have yet to be elucidated. Of particular interest are homologues of homeobox genes that in mouse and Drosophila are involved in patterning the developing central nervous system (CNS). Here, we report the cloning of an orthopedia (Otp)-related gene from Paracentrotus lividus, PlOtp. Otp is a single copy zygotic gene that presents a unique and highly restricted expression pattern. Transcripts were first detected at the mid-gastrula stage in two pairs of oral ectoderm cells located in a ventrolateral position, overlying primary mesenchyme cell (PMC) clusters. Increases in both transcript abundance and the number of Otp-expressing cells were observed at prism and pluteus stages. Otp transcripts are symmetrically distributed in a few ectodermal cells of the oral field. Labelled cells were observed close to sites of active skeletal rod growth (tips of the budding oral and anal arms), and at the juxtaposition of stomodeum and foregut. Chemicals known to perturb PMC patterning along animal-vegetal and oral-aboral axes altered the pattern of Otp expression. Vegetalization by LiCl caused a shift in Otp-expressing cells toward the animal pole, adjacent to shifted PMC aggregates. Nickel treatment induced expression of the Otp gene in an increased number of ectodermal cells, which adopted a radialized pattern. Finally, ectopic expression of Otp mRNA affected patterning along the oral-aboral axis and caused skeletal abnormalities that resembled those exhibited by nickel-treated embryos. From these results, we conclude that the Otp homeodomain gene is involved in short-range cell signalling within the oral ectoderm for patterning the endoskeleton of the larva through epithelial- mesenchymal interactions.
Targeted disruption of the homeobox transcription factor Nkx2-3 in mice results in postnatal lethality and abnormal development of small intestine and spleen
Authors: Pabst Oliver , Zweigerdt Robert , Arnold Hans-Henning 
Published: April 2021

ABSTRACT
The homeodomain transcription factor Nkx2-3 is expressed in gut mesenchyme and spleen of embryonic and adult mice. Targeted inactivation of the Nkx2-3 gene results in severe morphological alterations of both organs and early postnatal lethality in the majority of homozygous mutants. Villus formation in the small intestine appears considerably delayed in Nkx2-3−/− foetuses due to reduced proliferation of the epithelium, while massively increased growth of crypt cells ensues in surviving adult mutants. Interestingly, differentiated cell types of the intestinal epithelium are present in homozygous mutants, suggesting that Nkx2-3 is not required for their cell lineage allocation or migration-dependent differentiation. Hyperproliferation of the gut epithelium in adult mutants is associated with markedly reduced expression of BMP-2 and BMP-4, suggesting that these signalling molecules may be involved in mediating non-cell-autonomous control of intestinal cell growth.
Spleens of Nkx2-3 mutants are generally smaller and contain drastically reduced numbers of lymphatic cells. The white pulp appears anatomically disorganized, possibly owing to a homing defect in the spleen parenchyme. Moreover, some of the Nkx2-3 mutants exhibit asplenia. Taken together these observations indicate that Nkx2-3 is essential for normal development and functions of the small intestine and spleen.
Xenopus GDF6, a new antagonist of noggin and a partner of BMPs
Authors: Chang Chenbei , Hemmati-Brivanlou Ali 
Published: April 2021

Abstract
In Xenopus, ectodermal cell fates are determined by antagonistic interaction between the BMP subfamily of TGF-β ligands and the organizer-specific secreted factors (e.g. noggin, chordin and follistatin). Inhibition of BMP function by these factors can convert cells from an epidermal to a neural cell fate. In this study, we report that GDF6, a new member of the Xenopus TGF-β family, can function in antagonistic interaction with neural inducers. GDF6 induces epidermis and inhibits neural tissue in dissociated cells, and this activity is blocked by the presence of noggin. We demonstrate that GDF6 binds directly to the neural inducer noggin. Furthermore, we find that GDF6 and BMP2 can form heterodimers and the process seems to require cotranslation of the proteins in the same cells. In normal embryos, GDF6 and BMP2 are coexpressed in several places, including the edge of the neural plate at early neurula stages, suggesting that GDF6 may synergize with BMPs to regulate patterning of the ectoderm. Our data show for the first time that noggin can bind directly to and inhibit another TGF-β family member: GDF6. In addition, BMP and GDF6 heterodimers may play an important role in vivo to regulate cell fate determination and patterning.
The zebrafish diwanka gene controls an early step of motor growth cone migration
Authors: Zeller Jörg , Granato Michael 
Published: April 2021

Abstract
During vertebrate embryogenesis different classes of motor axons exit the spinal cord and migrate on common axonal paths into the periphery. Surprisingly little is known about how this initial migration of spinal motor axons is controlled by external cues. Here, we show that the diwanka gene is required for growth cone migration of three identified subtypes of zebrafish primary motoneurons. In diwanka mutant embryos, motor growth cone migration within the spinal cord is unaffected but it is strongly impaired as motor axons enter their common path to the somites. Chimera analysis shows that diwanka gene activity is required in a small set of myotomal cells, called adaxial cells. We identified a subset of the adaxial cells to be sufficient to rescue the diwanka motor axon defect. Moreover, we show that this subset of adaxial cells delineates the common axonal path prior to axonogenesis, and we show that interactions between these adaxial cells and motor growth cones are likely to be transient. The studies demonstrate that a distinct population of myotomal cells plays a pivotal role in the early migration of zebrafish motor axons and identify the diwanka gene as a somite-derived cue required to establish an axonal path from the spinal cord to the somites.
Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development
Authors: Lin Xinhua , Buff Eugene M. , Perrimon Norbert , Michelson Alan M. 
Published: April 2021

Abstract
The Drosophila sugarless and sulfateless genes encode enzymes required for the biosynthesis of heparan sulfate glycosaminoglycans. Biochemical studies have shown that heparan sulfate glycosaminoglycans are involved in signaling by fibroblast growth factor receptors, but evidence for such a requirement in an intact organism has not been available. We now demonstrate that sugarless and sulfateless mutant embryos have phenotypes similar to those lacking the functions of two Drosophila fibroblast growth factor receptors, Heartless and Breathless. Moreover, both Heartless- and Breathless-dependent MAPK activation is significantly reduced in embryos which fail to synthesize heparan sulfate glycosaminoglycans. Consistent with an involvement of Sulfateless and Sugarless in fibroblast growth factor receptor signaling, a constitutively activated form of Heartless partially rescues sugarless and sulfateless mutants, and dosage-sensitive interactions occur between heartless and the heparan sulfate glycosaminoglycan biosynthetic enzyme genes. We also find that overexpression of Branchless, the Breathless ligand, can partially overcome the requirement of Sugarless and Sulfateless for Breathless activity. These results provide the first genetic evidence that heparan sulfate glycosaminoglycans are essential for fibroblast growth factor receptor signaling in a well defined developmental context, and support a model in which heparan sulfate glycosaminoglycans facilitate fibroblast growth factor ligand and/or ligand-receptor oligomerization.
The midbrain-hindbrain boundary genetic cascade is activated ectopically in the diencephalon in response to the widespread expression of one of its components, the medaka gene Ol-eng2
Authors: Ristoratore Filomena , Carl Matthias , Deschet Karine , Richard-Parpaillon Laurent , Boujard Daniel , Wittbrodt Joachim , Chourrout Daniel , Bourrat Franck , Joly Jean-Stéphane 
Published: April 2021

Abstract
In vertebrates, the engrailed genes are expressed at early neurula stage in a narrow stripe encompassing the midbrain-hindbrain boundary (MHB), a region from which a peculiar structure, the isthmus, is formed. Knock-out experiments in mice demonstrated that these genes are essential for the development of this structure and of its derivatives. In contrast, little is known about the effect of an overexpression of engrailed genes in vertebrate development. Here we report the isolation of Ol-eng2, a medaka fish (Oryzias latipes) engrailed gene. We have monitored the effects of its widespread expression following mRNA injections in 1- and 2-cell medaka and Xenopus embryos. We found that the ectopic expression of Ol-eng2 predominantly results in an altered development of the anterior brain, including an inhibition of optic vesicle formation. No change in the patterns of mesencephalic and telencephalic markers were observed. In contrast, expressions of markers of the diencephalon were strongly repressed in injected embryos. Furthermore, the endogenous Ol-eng2, Pax2, Wnt1 and Fgf8, which are essential components of the MHB genetic cascade, were ectopically expressed in this region. Therefore, we propose that Ol-eng2 induces de novo formation of an isthmus-like structure, which correlates with the development of ectopic midbrain structures, including optic tectum. A competence of the diencephalon to change to a midbrain fate has been demonstrated in isthmic graft experiments. Our data demonstrate that this change can be mimicked by ectopic engrailed expression alone.