bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fkh5-deficient mice show dysgenesis in the caudal midbrain and hypothalamic mammillary body
Authors: Wehr Roland , Mansouri Ahmed , Maeyer Tine de , Gruss Peter 
Published: April 2021

ABSTRACT
The murine winged helix gene Fkh5 is specifically expressed in the developing central nervous system (CNS). Early embryonic Fkh5 expression is restricted to the mammillary body region of the caudal hypothalamus, midbrain, hindbrain and spinal cord. Postnatally, signals persist in specific nuclei of the mammillary body and in the midbrain. We generated Fkh5 deficient mice by homolo- gous recombination to assess its in vivo function. At birth, Fkh5-deficient mice are viable and indistinguishable from wild –type and Fkh5 heterozygous littermates. However, about one third die within the first two days and another fifth before weaning. Surviving Fkh5-deficient mice become growth retarded within the first week and remain smaller throughout their whole life span. Fkh5-deficient females on 129Sv ×C57BL/6 genetic background are fertile, but do not nurture their pups. More detailed analysis of Fkh5- deficient brains reveals distinct alterations in the CNS. In the midbrain, mutant mice exhibit reduced inferior colliculi and an overgrown anterior cerebellum. Further- more, the hypothalamic mammillary body of Fkh5- deficient brains lacks the medial mammillary nucleus. These results suggest that Fkh5 plays a major role during CNS development.
The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning
Authors: Kishimoto Yasuyuki , Lee Kyu-Ho , Zon Len , Hammerschmidt Matthias , Schulte-Merker Stefan 
Published: April 2021

ABSTRACT
Early dorsoventral pattern formation in vertebrate embryos is regulated by opposing activities of ventralizing bone morphogenetic proteins (BMPs) and dorsal-specific BMP antagonists such as Chordin, Noggin and Follistatin. Specific defects in early dorsoventral patterning have been recently found in a number of zebrafish mutants, which exhibit either a ventralized or dorsalized phenotype. One of these, the ventralized mutant chordino (originally called dino) is caused by a mutation in the zebrafish chordin homologue and interacts genetically with the dorsalized mutant swirl. In swirl mutant embryos, dorsal structures such as notochord and somites are expanded while ventral structures such as blood and nephros are missing. Here we demonstrate that the swirl phenotype is caused by mutations in the zebrafish bmp2 gene (zbmp2). While injection of mRNAs encoded by the mutant alleles has no ventralizing effect, injection of wild-type zbmp2 mRNA leads to a complete rescue of the swirl mutant phenotype. Fertile adult mutant fish were obtained, showing that development after gastrulation is not dependent on zbmp2 function. In addition zBMP2 has no maternal role in mesoderm induction. Our analysis shows that swirl/BMP2, unlike mouse BMP2 but like mouse BMP4, is required for early dorsoventral patterning of the zebrafish embryo.
Noggin acts downstream of Wnt and Sonic Hedgehog to antagonize BMP4 in avian somite patterning
Authors: Hirsinger Estelle , Duprez Delphine , Jouve Caroline , Malapert Pascale , Cooke Jonathan , Pourquié Olivier 
Published: April 2021

ABSTRACT
In the vertebrate embryo, the lateral compartment of the somite gives rise to muscles of the limb and body wall and is patterned in response to lateral-plate-derived BMP4. Activation of the myogenic program distinctive to the medial somite, i.e. relatively immediate development of the epaxial muscle lineage, requires neutralization of this lateral signal. We have analyzed the properties of molecules likely to play a role in opposing lateral somite specification by BMP4. We propose that the BMP4 antagonist Noggin plays an important role in promoting medial somite patterning in vivo. We demonstrate that Noggin expression in the somite is under the control of a neural-tube-derived factor, whose effect can be mimicked experimentally by Wnt1. Wnt1 is appropriately expressed in the neural tube. Furthermore, we show that Sonic Hedgehog is able to activate ectopic expression of Noggin resulting in the blocking of BMP4 specification of the lateral somite. Our results are consistent with a model in which Noggin activation lies downstream of the SHH and Wnt signaling pathways.
maelstrom is required for an early step in the establishment of Drosophila oocyte polarity: posterior localization of grk mRNA
Authors: Clegg Nigel J. , Frost Deanna M. , Larkin Michele Keller , Subrahmanyan Lakshman , Bryant Zev , Ruohola-Baker Hannele 
Published: April 2021

ABSTRACT
We describe a mutant, maelstrom, that disrupts a previously unobserved step in mRNA localization within the early oocyte, distinct from nurse-cell-to-oocyte RNA transport. Mutations in maelstrom disturb the localization of mRNAs for Gurken (a ligand for the Drosophila Egf receptor), Oskar and Bicoid at the posterior of the developing (stage 3-6) oocyte. maelstrom mutants display phenotypes detected in gurken loss-of-function mutants: posterior follicle cells with anterior cell fates, bicoid mRNA localization at both poles of the stage 8 oocyte and ventralization of the eggshell. These data are consistent with the suggestion that early posterior localization of gurken mRNA is essential for activation of the Egf receptor pathway in posterior follicle cells. Posterior localization of mRNA in stage 3-6 oocytes could therefore be one of the earliest known steps in the establishment of oocyte polarity. The maelstrom gene encodes a novel protein that has a punctate distribution in the cytoplasm of the nurse cells and the oocyte until the protein disappears in stage 7 of oogenesis.
A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing
Authors: Strigini Maura , Cohen Stephen M. 
Published: April 2021

ABSTRACT
The secreted protein Hedgehog (Hh) transmits a signal from posterior to anterior cells that is essential for limb development in insects and vertebrates. In Drosophila, Hh has been thought to act primarily to induce localized expression of Decapentaplegic and Wingless which in turn relay patterning cues at long range. We report here that Hh plays an additional role in patterning the wing. By replacing endogenous Hh activity with that of a membranetethered form of Hh, we show that Hh acts directly to pattern the central region of the wing, in addition to its role as an inducer of Dpp. Comparing the biological activities of secreted and membrane-tethered Hh provides evidence that Hh forms a local concentration gradient and functions as a concentration-dependent morphogen in the fly wing.
Interactions between the EGF receptor and DPP pathways establish distinct cell fates in the tracheal placodes
Authors: Wappner Pablo , Gabay Limor , Shilo Ben-Zion 
Published: April 2021

ABSTRACT
The formation of the tracheal network in Drosophila is driven by stereotyped migration of cells from the tracheal pits. No cell divisions take place during tracheal migration and the number of cells in each branch is fixed. This work examines the basis for the determination of tracheal branch fates, prior to the onset of migration. We show that the EGF receptor pathway is activated by localized processing of the ligand SPITZ in the tracheal placodes and is responsible for the capacity to form the dorsal trunk and visceral branch. The DPP pathway, on the contrary, is induced in the tracheal pit by local presentation of DPP from the adjacent dorsal and ventral ectodermal cells. This pathway patterns the dorsal and lateral branches. Elimination of both pathways blocks migration of all tracheal branches. Antagonistic interactions between the two pathways are demonstrated. The opposing activities of two pathways may refine the final determination of tracheal branch fates.
Increased cell death in rat blastocysts exposed to maternal diabetes in utero and to high glucose or tumor necrosis factor-α in vitro
Authors: Pampfer Serge , Vanderheyden Ivo , McCracken Jane E. , Vesela Jarmila , Hertogh René De 
Published: April 2021

ABSTRACT
The morphogenetic function of the transient phase of cell death that occurs during blastocyst maturation is not known but it is thought that its regulation results from a delicate balance between survival and lethal signals in the uterine milieu. In this paper, we show that blastocysts from diabetic rats have a higher incidence of dead cells than control embryos. Differential lineage staining indicated that increased nuclear fragmentation occurred mainly in the inner cell mass. In addition, terminal transferase-mediated dUTP nick end labeling (TUNEL) demonstrated an increase in the incidence of non-fragmented DNA-damaged nuclei in these blastocysts. Analysis of the expression of clusterin, a gene associated with apoptosis, by quantitative reverse transcription-polymerase chain reaction detected an increase in the steady-state level of its transcripts in blastocysts from diabetic rats. In situ hybridization revealed that about half the cells identified as expressing clusterin mRNA exhibited signs of nuclear fragmentation. In vitro experiments demonstrated that high D-glucose increased nuclear fragmentation, TUNEL labeling and clusterin transcription. Tumor necrosis factor-α(TNFα), a cytokine whose synthesis is up-regulated in the diabetic uterus, did not induce nuclear fragmentation nor clusterin expression but increased the incidence of TUNEL-positive nuclei. The data suggest that excessive cell death in the blastocyst, most probably resulting from the overstimulation of a basal suicidal program by such inducers as glucose and TNF-α, may be a contributing factor of the early embryopathy associated with maternal diabetes.
Segregation of myogenic lineages in Drosophila requires Numb
Authors: Gómez Mar Ruiz , Bate Michael 
Published: April 2021

ABSTRACT
Terminal divisions of myogenic lineages in the Drosophila embryo generate sibling myoblasts that found larval muscles or form precursors of adult muscles. Alternative fates adopted by sibling myoblasts are associated with distinct patterns of gene expression. Genes expressed in the progenitor cell are maintained in one sibling and repressed in the other. These differences depend on an asymmetric segregation of Numb between sibling cells. In numb mutants, muscle fates associated with repression are duplicated and alternative muscles are lost. If numb is overexpressed the reverse transformation occurs. Numb acts to block Notch-mediated repression of genes expressed in muscle progenitor cells. Thus asymmetric cell divisions are essential determinants of muscle fates during myogenesis in Drosophila
Chitin oligosaccharides can induce cortical cell division in roots of Vicia sativa when delivered by ballistic microtargeting
Authors: Schlaman Helmi R. M. , Gisel Andreas A. , Quaedvlieg Nicolette E. M. , Bloemberg Guido V. , Lugtenberg Ben J. J. , Kijne Jan W. , Potrykus Ingo , Spaink Herman P. , Sautter Christof 
Published: April 2021

ABSTRACT
Rhizobia, bacterial symbionts of leguminous plants, produce lipo-chitin oligosaccharide (LCO) signal molecules that can induce nodule organogenesis in the cortex of legume roots in a host-specific way. The multi-unsaturated fatty acyl and the O-acetyl moieties of the LCOs of Rhizobium leguminosarum biovar viciae were shown to be essential for obtaining root nodule induction in Vicia sativa plants. We have used ballistic microtargeting as a novel approach to deliver derivatives of the nodulation signal molecules inside the roots of V. sativa. This method offers the unique ability to introduce soluble compounds into the tissue at a small area. The mitogenic effect of microtargeting of chitin oligosaccharides, including an analysis of the influence of the chain length and modifications, was tested in a qualitative assay. The role of a cell division factor from the root stele, uridine, has also been examined in these experiments. The results show that O-acetylated chitin oligosaccharides can induce root cortical cell divisions when delivered by microtargeting. For this effect it is essential that uridine is co-targeted. The foci of cortical cell division were often similar to root nodule primordia. Anatomical examination also revealed chimeric structures that share characteristics with lateral root and nodule primordia. Our data favour a model in which the oligosaccharide moiety of the rhizobial LCO induces cortical cell division and the fatty acyl moiety plays a role in transport of the LCO into the plant tissue.
Induction of female Sex-lethal RNA splicing in male germ cells: implications for Drosophila germline sex determination
Authors: Hager Jeffrey H. , Cline Thomas W. 
Published: April 2021

ABSTRACT
With a focus on Sex-lethal (Sx1), the master regulator of Drosophila somatic sex determination, we compare the sex determination mechanism that operates in the germline with that in the soma. In both cell types, Sx1 is functional in females (2X2A) and nonfunctional in males (1X2A). Somatic cell sex is determined initially by a dose effect of X:A numerator genes on Sx1 transcription. Once initiated, the active state of Sx1 is maintained by a positive autoregulatory feedback loop in which SXL protein insures its continued synthesis by binding to Sx1 pre-mRNA and thereby imposing the productive (female) splicing mode. The gene splicing-necessary factor (snf), which encodes a component of U1 and U2 snRNPs, participates in this RNA splicing control. Here we show that an increase in the dose of snf+ can trigger the female Sx1 RNA splicing mode in male germ cells and can feminize triploid intersex (2X3A) germ cells. These snf+ dose effects are as dramatic as those of X:A numerator genes on Sx1 in the soma and qualify snf as a numerator element of the X:A signal for Sx1 in the germline. We also show that female-specific regulation of Sx1 in the germline involves a positive autoregulatory feedback loop on RNA splicing, as it does in the soma. Neither a phenotypically female gonadal soma nor a female dose of X chromosomes in the germline is essential for the operation of this feedback loop, although a female X-chro-mosome dose in the germline may facilitate it. Engagement of the Sx1 splicing feedback loop in somatic cells invariably imposes female development. In contrast, engagement of the Sx1 feedback loop in male germ cells does not invariably disrupt spermatogenesis; nevertheless, it is premature to conclude that Sx1 is not a switch gene in germ cells for at least some sex-specific aspects of their differentiation. Ironically, the testis may be an excellent organ in which to study the interactions among regulatory genes such as Sx1, snf, ovo and otu which control female-specific processes in the ovary.
A role for netrin-1 in the guidance of cortical efferents
Authors: Métin Christine , Deléglise Delphine , Serafini Tito , Kennedy Timothy E. , Tessier-Lavigne Marc 
Published: April 2021

ABSTRACT
An intermediate target for axons leaving the cerebral cortex in embryonic mammals is the ganglionic eminence (GE), the embryonic precursor of the basal ganglia. The cues that direct these axons over the initial portion of their trajectory are not well understood, but could include both short-range and long-range attractants and repellents. In the present study, we provide evidence that corticofugal axons might be guided at least partly by a diffusible factor or factors originating in the lateral GE and the sulcus between the lateral and medial ridges of the GE (ISS), as well as evidence implicating the axonal chemoattractant netrin-1 in mediating these effects.
Explants of lateral GE and ISS obtained from E12.5 and E13.5 mouse forebrain have a strong effect on both the outgrowth and orientation of corticofugal axons when cultured at a distance with explants of embryonic cortex in collagen gels. Netrin-1 mRNA is detected in these target tissues by in situ hybridization, and both netrin-1 protein and heterologous cells secreting netrin-1 can mimic the outgrowth-promoting effect of these target tissues in vitro. Furthermore, the growth of corticofugal axons is oriented toward an ectopic source of netrin-1 in vitro, and a function blocking anti-netrin-1 antiserum specifically abolishes the cortical axon outgrowth elicited by explants of lateral GE and the ISS in collagen gel cocultures.
Taken together, these results suggest a role for netrin-1 in the attraction at a distance of early cortical axons by the GE. Thus in mammals – as is also observed in nematodes – the development of non-commissural projections in anterior regions of the embryo might be directed by mechanisms similar to those involved in directing the development of commissural projections in more posterior regions of the central nervous system.
Positive and negative DNA sequence elements are required to establish the pattern of Pax3 expression
Authors: Natoli Thomas A. , Ellsworth Mary Kay , Wu Chuanzhen , Gross Kenneth W. , Pruitt Steven C. 
Published: April 2021

ABSTRACT
The transcription start site and DNA sequence elements required for the induction of Pax3 expression in differentiating P19 embryonal carcinoma cells have been localized. These elements consist of a promoter and additional elements located within 1.6 kbp 5′ to the transcription start site. Sequence elements within this 1.6 kbp region are also sufficient to mediate the induction and dorsal restriction of Pax3 in the neural tube and somites of transgenic mice throughout the hindbrain and trunk. Additional elements required for expression anterior to the hindbrain and in migrating myoblasts are located within 14 kbp 5′ to the transcription start site. This region also contains element(s) that repress Pax3 expression in the ventral body wall mesoderm of the tail bud.
The Xenopus homolog of Drosophila Suppressor of Hairless mediates Notch signaling during primary neurogenesis
Authors: Wettstein Daniel A. , Turner David L. , Kintner Chris 
Published: April 2021

ABSTRACT
The X-Notch-1 receptor, and its putative ligand, X-Delta-1, are thought to mediate an inhibitory cell-cell interaction, called lateral inhibition, that limits the number of primary neurons that form in Xenopus embryos. The expression of Xenopus ESR-1, a gene related to Drosophila Enhancer of split, appears to be induced by Notch signaling during this process. To determine how the activation of X-Notch-1 induces ESR-1 expression and regulates primary neurogenesis, we isolated the Xenopus homolog of Suppressor of Hairless (X-Su(H)), a component of the Notch signaling pathway in Drosophila. Using animal cap assays, we show that X-Su(H) induces ESR-1 expression, perhaps directly, when modified by the addition of ankyrin repeats. Using a DNA binding mutant of X-Su(H), we show that X-Su(H) activity is required for induction of ESR-1. Finally, expression of the DNA binding mutant in embryos leads to a neurogenic phenotype as well as increased expression of both X-Delta-1 and XNGNR1, a proneural gene expressed during primary neurogenesis. These results suggest that activation of X-Su(H) is a key step in the Notch signaling pathway during primary neurogenesis in Xenopus embryos.
A genetic pathway for regulation of tra-2 translation
Authors: Goodwin Elizabeth B. , Hofstra Karen , Hurney Carol A. , Mango Susan , Kimble Judith 
Published: April 2021

ABSTRACT
In Caenorhabditis elegans, the tra-2 sex-determining gene is regulated at the translational level by two 28 nt direct repeat elements (DREs) located in its 3′ untranslated region (3′UTR). DRF is a factor that binds the DREs and may be a trans-acting translational regulator of tra-2. Here we identify two genes that are required for the normal pattern of translational control. A newly identified gene, called laf-1, is required for translational repression by the tra-2 3′UTR. In addition, the sex-determining gene, tra-3, appears to promote female development by freeing tra-2 from laf-1 repression. Finally, we show that DRF activity correlates with translational repression of tra-2 during development and that tra-3 regulates DRF activity. We suggest that tra-3 may promote female development by releasing tra-2 from translation repression by laf-1 and that translational control is important for proper sex determination – both in the early embryo and during postembryonic development.
Conservation of Pax-6 in a lower chordate, the ascidian Phallusia mammillata
Authors: Glardon Sacha , Callaerts Patrick , Halder Georg , Gehring Walter J. 
Published: April 2021

ABSTRACT
The Pax-6 genes of vertebrates and invertebrates encode transcription factors with both a paired domain and a homeodomain. They are expressed in the developing eye and in the central nervous system. Loss-of-function mutations in mammals and in flies result in a reduction or absence of eyes and targeted expression of the Drosophila and the mouse Pax-6 genes induces ectopic eye structures in Drosophila. These findings lead to the proposal that the morphogenesis of the different types of eyes is controlled by a Pax-6-dependent genetic pathway and that the various eye types are of monophyletic origin. We have isolated a Pax-6 homologous gene from the ascidian Phallusia mammillata, because ascidians occupy an important position in early chordate evolution. Furthermore, the Phallusia larva has a simple photosensitive ocellus. Phallusia Pax-6 shares extensive sequence identity and conserved genomic organization with the known Pax-6 genes of vertebrates and invertebrates. Expression of Phallusia Pax-6 is first detected at late gastrula stages in distinct regions of the developing neural plate. At the tailbud stage, it is expressed in the spinal cord and the brain vesicle, where the sensory organs (ocellus and otolith) form, suggesting an important function in their development. Ectopic expression of the ascidian Pax-6 gene in Drosophila leads to the induction of supernumerary eyes indicating a highly conserved gene regulatory function for Pax-6 genes.
Ftz-F1 is a cofactor in Ftz activation of the Drosophila engrailed gene
Authors: Florence Brian , Guichet Antoine , Ephrussi Anne , Laughon Allen 
Published: April 2021

ABSTRACT
The fushi tarazu pair-rule gene is required for the formation of alternating parasegmental boundaries in the Drosophila embryo. fushi tarazu encodes a homeodomain protein necessary for transcription of the engrailed gene in even-numbered parasegments. Here we report that, within an engrailed enhancer, adjacent and conserved binding sites for the Fushi tarazu protein and a cofactor are each necessary, and together sufficient, for transcriptional activation. Footprinting shows that the cofactor site can be bound specifically by Ftz-F1, a member of the nuclear receptor superfamily. Ftz-F1 and the Fushi tarazu homeodomain bind the sites with 4-to 8-fold cooperativity, suggesting that direct contact between the two proteins may contribute to target recognition. Even parasegmental reporter expression is dependent on Fushi tarazu and maternal Ftz-F1, suggesting that these two proteins are indeed the factors that act upon the two sites in embryos. The two adjacent binding sites are also required for continued activity of the engrailed enhancer after Fushi tarazu protein is no longer detectable, including the period when engrailed, and the enhancer, become dependent upon wingless. We also report the existence of a separate negative regulatory element that apparently responds to odd-skipped.