bluuebunny/crossref_metadata_2025_split huggingface dataset:
valentino: a zebrafish gene required for normal hindbrain segmentation
Authors: Moens Cecilia B. , Yan Yi-Lin , Appel Bruce , Force Allan G. , Kimmel Charles B. 
Published: April 2021

ABSTRACT
Mutational analysis can serve both to identify new genes essential for patterning embryonic development and to determine their functions. Here we describe the identifica-tion and phenotypic characterization of alleles of valentino, which we recovered in a genetic screen that sought to identify mutations in the zebrafish that disrupt region-specific gene expression patterns in the embryonic brain. valentino is required for normal hindbrain segmentation and the hindbrain of valentino mutant embryos is shortened by the length of one rhombomere. We demon-strate that valentino is required cell-autonomously in the development of rhombomeres 5 and 6, and propose that valentino functions in the subdivision and expansion of a common precursor region in the presumptive hindbrain into the definitive rhombomeres 5 and 6. These results provide genetic evidence for a two-segment periodicity in the hindbrain and suggest that this periodicity arises sequentially, through the specification and later subdivi-sion of a two-rhombomere unit, or ‘protosegment’.
Xenopus VegT RNA is localized to the vegetal cortex during oogenesis and encodes a novel T-box transcription factor involved in mesodermal patterning
Authors: Zhang Jian , King Mary Lou 
Published: April 2021

ABSTRACT
An RNA localized to the vegetal cortex of Xenopus oocytes encodes a novel T-box protein (VegT) capable of inducing either dorsal or posterior ventral mesoderm at different times in development. VegT is a nuclear protein and its C-terminal domain can activate transcription in a yeast reporter assay, observations consistent with VegT functioning as a transcription factor. Zygotic expression is dynamic along the dorsoventral axis, with transcripts first expressed in the dorsal marginal zone. By the end of gas-trulation, VegT is expressed exclusively in posterior ventral and lateral mesoderm and is excluded from the notochord. Later expression is confined to a subset of Rohon-Beard cells, a type of primary sensory neuron. In animal cap assays, VegT is capable of converting prospective ectoderm into ventral lateral mesoderm. Such ectopic expression of VegT induces its own expression as well as that of Xwnt-8 in caps, suggesting that a Wnt pathway may be involved. Mis-expression of VegT in dorsal animal blastomeres fated to contribute to brain suppresses head formation. Our results suggest that VegT is a localized transcription factor, which operates sequentially in several developmental pathways during embryogenesis, including dorsoventral and posterior patterning of mesoderm.
The Xenopus T-box gene, Antipodean, encodes a vegetally localised maternal mRNA and can trigger mesoderm formation
Authors: Stennard Fiona , Carnac Gilles , Gurdon J. B. 
Published: April 2021

ABSTRACT
We have used differential display to identify genes inducible by activin and isolated a novel member of the T-box gene family that includes the Xenopus genes Xbrachyury and Eomesodermin. Here we show that this novel gene is unique within the T-box family because it is maternally expressed at a high level. Furthermore, it belongs to a rare class of maternal mRNAs in Xenopus that are localised to the vegetal hemisphere of the egg and we have therefore named it Antipodean. We show here that low amounts of Antipodean injected into ectoderm (animal cap cells) strongly induce pan mesodermal genes such as Xbrachyury and ventral mesodermal genes such as Xwnt-8. Overexpression of Antipodean generates mesoderm of ventral character, and induces muscle only weakly. This property is consistent with the observed late zygotic Antipodean mRNA expression in the posterior paraxial mesoderm and ventral blastopore, and its exclusion from the most dorsal mesodermal structure, the notochord. Antipodean is induced by several molecules of the TGF-β class, but in contrast to Xbrachyury, not by bFGF. This result suggests that the expression of these T-box genes may be under the control of different regulatory pathways. Finally, we demonstrate that Antipodean and Eomesoder-min induce each other and both are able to induce Xbrachyury. The early zygotic expression of Antipodean is not induced by Xbrachyury, though later it is to some extent. Considering its maternal content, Antipodean could initiate a cascade of T-box gene activations. The expression of these genes may, in turn, sustain each other’s expression to define and maintain the mesoderm identity in Xenopus.
Prenatal and postnatal requirements of NT-3 for sympathetic neuroblast survival and innervation of specific targets
Authors: ElShamy Wael M. , Linnarsson Sten , Lee Kuo-Fen , Jaenisch Rudolf , Ernfors Patrik 
Published: April 2021

ABSTRACT
Postnatal homozygous neurotrophin-3 mutant mice display a loss of about half the sympathetic superior cervical ganglion (SCG) neurons (Ernfors, P., Lee, K.-F., Kucera, J. and Jaenisch, R. (1994a) Cell 77, 503-512; Farinas, I., Jones, K. R., Backus, C., Wang, X. Y. and Reichardt, L. F. (1994) Nature 369, 658-661). We found that this loss is caused by excessive apoptosis of sympathetic neuroblasts leading to a failure to generate a normal number of neurons during neurogenesis. NT-3 was also found to be required postnatally. In Nt-3−/− mice, sympathetic fibers failed to invade pineal gland and external ear postnatally; whereas other targets of the external and internal carotid nerves, including the submandibular gland and the iris, displayed a normal complement of sympathetic innervation. Sympathetic fibers of mice carrying one functional copy of the Nt-3 gene (Nt-3+/− mice) invaded the pineal gland, but failed to branch and form a ground plexus. Cultured neonatal sympathetic neurons responded to NT-3 by neurite outgrowth and mRNA upregulation of the NT-3 receptor, trkC. Exogenously administered NT-3 promoted sympathetic growth and rescued the sympathetic target deficit of the mutant mice. We conclude that NT-3 is required for the survival of sympathetic neuroblasts during neurogenesis and for sympathetic innervation and branching in specific targets after birth.
Pax-3 is necessary for migration but not differentiation of limb muscle precursors in the mouse
Authors: Daston George , Lamar Elise , Olivier Marc , Goulding Martyn 
Published: April 2021

ABSTRACT
The limb muscles of vertebrates are derived from precursor cells that migrate from the lateral edge of the dermomyotome into the limb bud. Previous studies have shown that the paired domain-containing transcription factor Pax-3 is expressed in the limb in cells that are precursors for limb muscles (Williams, B. and Ordahl, C. P. (1994) Development 120, 785–796). In splotch (Pax-3–) embryos, the limb muscles fail to develop and cells expressing Pax-3 are no longer found in the limb. In this paper we have analyzed the role of Pax-3 in the migration and subsequent differentiation of limb muscle precursors. By labeling somites adjacent to the prospective forelimb with the lipophilic dye DiI, we have shown that cells derived from these somites do not migrate into the limbs of splotch mice. The failure of limb muscle precursors to invade the limb in splotch mice is associated with the absence of c-met expression in premigratory cells, together with a change in the morphology of the ventral dermomyotome. In addition, we have shown the lateral half of somites derived from day E9.25 splotch embryos can undergo muscle differentiation when grafted into the limb bud of stage 20 chick host embryos. Our results indicate that Pax-3 regulates the migration of limb muscle precursors into the limb and is not required for cells in the lateral somite to differentiate into muscle.
Expression of type 1 inositol 1,4,5-trisphosphate receptor during axogenesis and synaptic contact in the central and peripheral nervous system of developing rat
Authors: Dent Myrna A. R. , Raisman Geoff , Lai F. Anthony 
Published: April 2021

ABSTRACT
Release of intracellular Ca2+ is triggered by the second messenger inositol 1,4,5-trisphosphate, which binds to the inositol 1,4,5-trisphosphate receptor and gates the opening of an intrinsic calcium channel in the endoplasmic reticulum. In order to understand the importance of this mechanism in development, we have examined the distribution of the type 1 inositol 1,4,5-trisphosphate receptor during development, in some areas of the rat brain and spinal cord and in peripheral neurons, using in situ hybridization and immunohistochemistry. In brain, we find that type 1 inositol 1,4,5-trisphosphate receptor is expressed in neurons from very early in development; low levels of expression are first detected after the neurons have migrated to their final positions, when they start to differentiate and begin axonal growth. Increasing levels of expression are observed later in development, during the time of synaptogenesis and dendritic contact. Glial cells do not express type 1 inositol 1,4,5-trisphosphate receptor, except for a transient period of expression, probably by oligodendrocytes, in developing fibre tracts during the onset of myelination. In contrast with the brain, both grey and white matter of the spinal cord express type 1 inositol 1,4,5-trisphosphate receptor throughout development, and it remains present in the adult spinal cord. We also show, for the first time, that type 1 inositol 1,4,5-trisphosphate receptor is expressed in the peripheral nervous system. Strong labelling was observed in the dorsal root ganglia and during development this expression seems to coincide with the onset of axogenesis. These results suggest that type 1 inositol 1,4,5-trisphosphate receptor may be involved in the regulatory mechanism controlling Ca2+ levels in neurons during the periods of cell differentiation, axogenesis and synaptogenesis.
Analysis of cell movement during the culmination phase of Dictyostelium development
Authors: Dormann Dirk , Siegert Florian , Weijer Cornelis J. 
Published: April 2021

ABSTRACT
Co-ordinated cell movement of tens of thousands of cells and periodic signals characterise the multicellular development of the cellular slime mould Dictyostelium discoideum. We investigated cell movement by analysing timelapse video recordings made during the slug stage and the culmination phase of Dictyostelium development. Slugs viewed from the side showed an even, straight forward movement with the tip slightly raised in the air. Slugs, that had migrated for a prolonged period of time either culminated or showed a behaviour best described as abortive culmination. Culmination is initiated by a local aggregation of anterior-like cells at the base of the slug at the prestalkprespore boundary, where they form a stationary mass of cells. Prespore cells continue to move forward over this stationary pile and, as a result, are lifted into the air. The stationary group of anterior-like cells thereby end up to the back of the slug. At this point the slug either falls back on the agar surface or continues culmination. If the slug continues to migrate these cells regain motility, move forward to the prespore-prestalk boundary and form a new pile again. In the case of culmination the neutral red stained cells in the pile move to the back of the slug and form a second signalling centre beside the tip. Both centres are characterised by vigorous rotational cell movement. The cells belonging to the basal centre will form the basal disc and the lower cup in the fruiting body. The upper cup will be formed by the prestalk cells rotating most vigorously at the prestalk-prespore boundary. The remaining neutral red stained anterior-like cells in the prespore zone sort either to the upper or lower organising centre in the fruiting body.
Late effects of retinoic acid on neural crest and aspects of rhombomere identity
Authors: Gale Emily , Prince Victoria , Lumsden Andrew , Clarke Jon , Holder Nigel , Maden Malcolm 
Published: April 2021

ABSTRACT
We exposed st.10 chicks to retinoic acid (RA), both globally, and locally to individual rhombomeres, to look at its role in specification of various aspects of hindbrain derived morphology. Previous studies have looked at RA exposure at earlier stages, during axial specification. Stage 10 is the time of morphological segmentation of the hindbrain and is just prior to neural crest migration. Rhombomere 4 localised RA injections result in specific alterations of pathways some crest cells that normally migrate to sites of differentiation of neurogenic derivatives. The r4 crest cells that give rise to mesenchymal derivatives are unaffected. In addition, r4 gene expression is also partially altered by RA; within 6 hours of r4 exposure to RA, ectopic expression of Krox-20 is seen in r4 and Hoxb-1 expression is lost while Hoxa-2 expression continues normally. When we examined these RA-treated animals later in development, they showed an anterior displacement of the facial ganglion in addition to a mis-direction of the extensions of its distal axons and a dramatic decrease in the number of contralateral vestibuloacoustic neurons normally seen in r4. Only this r4-specific neuronal type is affected in r4; the motor neuron projections seem normal in experimental animals. The specificity of this result, combined with the loss of Hoxb-1 expression in r4 and the work by Krumlauf and co-workers showing gain of contralateral neurons co-localised with ectopic Hoxb-1 expression, indicates a role for Hoxb-1 and RA in the specification of this cell type in normal development. These results suggest that RA, at st.10, is able to affect some aspects of segment identity while leaving others unchanged.
Mos is required for MAP kinase activation and is involved in microtubule organization during meiotic maturation in the mouse
Authors: Verlhac Marie-Hélène , Kubiak Jacek Z. , Weber Michèle , Géraud Gérard , Colledge William H. , Evans Martin J. , Maro Bernard 
Published: April 2021

ABSTRACT
Mos is normally expressed during oocyte meiotic maturation in vertebrates. However, apart from its cytostatic factor (CSF) activity, its precise role during mouse meiosis is still unknown. First, we analyzed its role as a MAP kinase kinase kinase. Mos is synthesized concomitantly with the activation of MAP kinase in mouse oocytes. Moreover, MAP kinase is not activated during meiosis in oocytes from mos–/– mice. This result implies that Mos is necessary for MAP kinase activation in mouse oocytes. Raf-1, another MAP kinase kinase kinase, is already present in immature oocytes, but does not seem to be active when MAP kinase is activated. Moreover, the absence of MAP kinase activation in mos–/– oocytes demonstrates that Raf-1 cannot compensate for the lack of Mos. These results suggest that Raf1 is not involved in MAP kinase activation. Second, we analyzed the organization of the microtubules and chromosomes in oocytes from mos–/– mice. We observed that during the transition between two meiotic M-phases, the microtubules and chromosomes evolve towards an interphase-like state in mos–/– oocytes, while in the control mos+/− oocytes they remain in an M-phase configuration, as in the wild type. Moreover, after spontaneous activation, the majority of mos–/– oocytes are arrested for at least 10 hours in a third meiotic M-phase where they exhibit monopolar half-spindles. These observations present the first evidence, in intact oocytes, of a role for the Mos/…/MAP kinase cascade in the control of microtubule and chromatin organization during meiosis.
Dysgenesis of cephalic neural crest derivatives in Pax7−/− mutant mice
Authors: Mansouri Ahmed , Stoykova Anastasia , Torres Miguel , Gruss Peter 
Published: April 2021

ABSTRACT
Pax7 is a member of the paired box containing gene family. Its expression pattern suggests a function in cephalic neural crest derivatives, skeletal muscle and central nervous system development. To understand the role of Pax7 during mouse embryogenesis, we used the homologous recombination technique in embryonic stem cells and generated Pax7–/– mice. Homozygous animals are born but die shortly after weaning. They exhibit malformations in facial structures involving the maxilla and nose. Our analysis suggests that the observed phenotype is due to a cephalic neural crest defect. No obvious phenotype could be detected in the central nervous system and skeletal muscle. Functional redundancy between Pax7 and Pax3 is discussed.
Allele-specific in situ hybridization (ASISH) analysis: a novel technique which resolves differential allelic usage of H19 within the same cell lineage during human placental development
Authors: Adam Gail I. R. , Cui Hengmi , Miller Stephen J. , Flam Folke , Ohlsson Rolf 
Published: April 2021

ABSTRACT
Precursory studies of H19 transcription during human foetal development have demonstrated maternally derived monoallelic expression. Analyses in extra-embryonic tissues, however, have been more equivocal, with discernible levels of expression of the paternal allele of H19 documented in the first trimester placenta. By refining the in situ hybridization technique we have developed an assay to enable the functional imprinting status of H19 to be determined at the cellular level. This assay involves the use of oligonucleotide DNA probes that are able to discriminate between allelic RNA transcripts containing sequence polymorphisms. Biallelic expression of H19 is confined to a subpopulation of cells of the trophoblast lineage, the extravillous cytotrophoblast, while the mesenchymal stroma cells maintain the imprinted pattern of monoallelic expression of H19 throughout placental development. This data demonstrates that the low level of paternal H19 expression previously detected in normal human placenta is not due to a random loss of functional imprinting, but appears to result from a developmentally regulated cell type-specific activation of the paternal allele. In addition, biallelic expression of H19 does not seem to affect the functional imprinting of the insulin-like growth factor II gene, which is monoallelically expressed at relatively high levels in the extra-villous cytotrophoblasts. These results imply that the allelic usage of these two genes in normal human placental development may not be directly analogous to the situation previously documented in the mouse embryo.
Rhombomere of origin determines autonomous versus environmentally regulated expression of Hoxa3 in the avian embryo
Authors: Saldivar Jose R. , Krull Catherine E. , Krumlauf Robb , Ariza-McNaughton Linda , Bronner-Fraser Marianne 
Published: April 2021

ABSTRACT
We have investigated the pattern and regulation of Hoxa3 expression in the hindbrain and associated neural crest cells in the chick embryo, using whole mount in situ hybridization in conjunction with DiI labeling of neural crest cells and microsurgical manipulations. Hoxa3 is expressed in the neural plate and later in the neural tube with a rostral border of expression corresponding to the boundary between rhombomeres (r) 4 and 5. Initial expression is diffuse and becomes sharp after boundary formation. Hoxa3 exhibits uniform expression within r5 after formation of rhombomeric borders. Cell marking experiments reveal that neural crest cells migrating caudally, but not rostrally, from r5 and caudally from r6 express Hoxa3 in the normal embryo. Results from transposition experiments demonstrate that expression of Hoxa3 in r5 neural crest cells is not strictly cell-autonomous. When r5 is transposed with r4 by rostrocaudal rotation of the rhombomeres, Hoxa3 is expressed in cells migrating lateral to transposed r5 and for a short time, in condensing ganglia, but not by neural crest within the second branchial arch. Since DiI-labeled cells from transposed r5 are present in the second arch, Hoxa3-expressing neural crest cells from r5 appear to down-regulate their Hoxa3 expression in their new environment. In contrast, when r6 is transposed to the position of r4 after boundary formation, Hoxa3 is maintained in both migrating neural crest cells and those positioned within the second branchial arch and associated ganglia. These results suggest that Hoxa3 expression is cellautonomous in r6 and its associated neural crest. Our results suggest that neural crest cells expressing the same Hox gene are not equivalent; they respond differently to environmental signals and exhibit distinct degrees of cell autonomy depending upon their rhombomere of origin.
The Drosophila stonewall gene encodes a putative transcription factor essential for germ cell development
Authors: Clark Kathleen A. , McKearin Dennis M. 
Published: April 2021

ABSTRACT
The differentiation of Drosophila germ cells is a useful model for studying mechanisms of cell specification. We report the identification of a gene, stonewall, that is required for germ cell development. Mutations in stonewall block proper oocyte differentiation and frequently cause the presumptive oocyte to develop as a nurse cell. Eventually, germ cells degenerate apoptotically. Stonewall is a germ cell nuclear protein; Stonewall has a DNA binding domain that shows similarities to the Myb and Adf-1 transcription factors and has other features that suggest that it is a transcription activating factor. We suggest that Stonewall transcriptional regulation is essential in cystocytes for maturation into specialized nurse cells and oocyte.
The Drosophila tissue polarity gene inturned acts cell autonomously and encodes a novel protein
Authors: Park Woo Jin , Liu Jingchun , Sharp Edward J. , Adler Paul N. 
Published: April 2021

ABSTRACT
Mutations in the inturned (in) gene result in abnormal wing hair polarity and in many wing cells forming two or more hairs instead of the normal single hair. We have generated genetic mosaics in a number of different experiments and find that the in gene is required in all regions of the wing and that it functions in a cell autonomous fashion. We report the molecular cloning of the in gene, the molecular mapping of in mutations and the isolation and sequencing of an in cDNA clone. The in gene encodes a novel protein whose sequence suggests it will be membrane bound. The ability of an in cDNA, the expression of which is driven by the basal activity of the hsp70 promoter to rescue an in mutation suggests that patterned expression of in is unlikely to play a role in the function of this gene.