bluuebunny/crossref_metadata_2025_split huggingface dataset:
DPP controls tracheal cell migration along the dorsoventral body axis of the Drosophila embryo
Authors: Vincent Stéphane , Ruberte Esther , Grieder Nicole C. , Chen Chao-Kung , Haerry Theo , Schuh Reinhard , Affolter Markus 
Published: April 2021

ABSTRACT
We report that DPP signaling is required for directed tracheal cell migration during Drosophila embryogenesis. The failure of tracheal cells to receive the DPP signal from adjacent dorsal and ventral cells results in the absence of dorsal and ventral migrations. Ectopic DPP signaling can reprogram cells in the center of the placode to adopt a dorsoventral migration behavior. The effects observed in response to ectopic DPP signaling are also observed upon the tracheal-specific expression of a constitutive active DPP type I receptor (TKVQ253D), indicating that the DPP signal is received and transmitted in tracheal cells to control their migration behavior. DPP signaling determines localized gene expression patterns in the developing tracheal placode, and is also required for the dorsal expression of the recently identified BRANCHLESS (BNL) guidance molecule, the ligand of the BREATHLESS (BTL) receptor. Thus, DPP plays a dual role during tracheal cell migration. It is required to control the dorsal expression of the BNL ligand; in addition, the DPP signal recruits groups of dorsal and ventral tracheal cells and programs them to migrate in dorsal and ventral directions.
Cellularization in locust embryos occurs before blastoderm formation
Authors: Ho Karen , Dunin-Borkowski Olga M. , Akam Michael 
Published: April 2021

ABSTRACT
In Drosophila intracellular gradients establish the pattern of segmentation by controlling gene expression during a critical syncytial stage, prior to cellularization. To investigate whether a similar mechanism may be exploited by other insects, we examined the timing of cellularization with respect to blastoderm formation in an insect with extreme short-germ development, the African desert locust, Schistocerca gregaria. Using light and electron microscopic techniques, we show that the islands of cytoplasm surrounding cleavage nuclei are largely isolated from their neighbours, allowing cleavage to proceed asynchronously. Within a short time of their arrival at the surface and prior to blastoderm formation, nuclei become surrounded by complete cell membranes that block the free uptake of dye (10,000 kDa) from the yolk. Our results imply that the formation of the blastoderm disc involves the aggregation of cells at the posterior pole of the egg and not the migration of nuclei within a syncytial cytoplasm. These findings suggest that the primary cleavage syncytium does not play the same role in patterning the locust embryo as it does in Drosophila. However, we do identify a syncytial nuclear layer that underlies the forming blastoderm and remains in continuity with the yolk.
Positional apoptosis during vertebrate CNS development in the absence of endogenous retinoids
Authors: Maden Malcolm , Graham Anthony , Gale Emily , Rollinson Chris , Zile Maija 
Published: April 2021

ABSTRACT
We have previously shown that quail embryos that develop in the absence of vitamin A have severe defects in their central nervous system. One defect is a completely missing posterior hindbrain. Here we have studied how this comes about by examining cell death using a wholemount technique. In these A− embryos we observe two narrow bands of ectopic apoptosis. One is in the mesenchyme in the region of the first somite and occurs at the 4–6 somite stage, before neural tube closure. The second band follows immediately afterwards and occurs in the neuroepithelium of the presumptive posterior hindbrain at the 6-8 somite stage. Electron microscopy shows that the dying neuroepithelial cells exhibit the characteristics of apoptosis. Rescuing the embryos by injecting retinol before gastrulation completely prevents these apoptotic events. In an effort to identify some of the genes that may be involved in the apoptotic pathway we show that Msx-2 is upregulated in the apoptotic neuroepithelium and thus may be involved, whereas Bmp-4 is not altered and thus presumably not involved. Since these apoptotic event take place at the time of specification of axial identity and segmentation in the mesenchyme and neuroepithelium we conclude that these cells die because they are wrongly specified in terms of their rostrocaudal position, a novel phenomenon which we refer to as positional apoptosis.
Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak
Authors: Ciruna Brian G. , Schwartz Lois , Harpal Kendraprasad , Yamaguchi Terry P. , Rossant Janet 
Published: April 2021

ABSTRACT
Fibroblast growth factor (FGF) signaling has been implicated in the patterning of mesoderm and neural lineages during early vertebrate development. In the mouse, FGF receptor-1 (FGFR1) is expressed in an appropriate spatial and temporal manner to be orchestrating these functions. Mouse embryos homozygous for a mutated Fgfr1 allele (fgfr1Δtmk) die early in development, show abnormal growth and aberrant mesodermal patterning. We have performed a chimeric analysis to further study FGFR1 function in the morphogenesis and patterning of the mesodermal germ layer at gastrulation. At E9.5, fgfr1Δtmk/fgfr1Δtmk cells showed a marked deficiency in their ability to contribute to the extra-embryonic, cephalic, heart, axial and paraxial mesoderm, and to the endoderm of chimeric embryos. Analysis at earlier stages of development revealed that fgfr1Δtmk/fgfr1Δtmk cells accumulated within the primitive streak of chimeric embryos, and consequently failed to populate the anterior mesoderm and endodermal lineages at their inception. We suggest that the primary defect associated with the fgfr1Δtmk mutation is a deficiency in the ability of epiblast cells to traverse the primitive streak. fgfr1Δtmk/fgfr1Δtmk cells that accumulated within the primitive streak of chimeric embryos tended to form secondary neural tubes. These secondary neural tubes were entirely fgfr1Δtmk/fgfr1Δtmk cell derived. The adoption of ectopic neural fate suggests that normal morphogenetic movement through the streak is essential not only for proper mesodermal patterning but also for correct determination of mesodermal/neurectodermal cell fates.
goosecoid and HNF-3β genetically interact to regulate neural tube patterning during mouse embryogenesis
Authors: Filosa Stefania , Rivera-Pérez Jaime A. , Gómez Aitana Perea , Gansmuller Anne , Sasaki Hitoshi , Behringer Richard R. , Ang Siew-Lan 
Published: April 2021

ABSTRACT
The homeobox gene goosecoid (gsc) and the winged-helix gene Hepatic Nuclear Factor-3β (HNF-3β) are co-expressed in all three germ layers in the anterior primitive streak and at the rostral end of mouse embryos during gastrulation. In this paper, we have tested the possibility of functional synergism or redundancy between these two genes during embryogenesis by generating double-mutant mice for gsc and HNF-3β. Double-mutant embryos of genotype gsc−/−;HNF-3β+/− show a new phenotype as early as embryonic days 8.75. Loss of Sonic hedgehog (Shh) and HNF-3β expression was observed in the notochord and ventral neural tube of these embryos. These results indicate that gsc and HNF-3β interact to regulate Shh expression and consequently dorsal-ventral patterning in the neural tube. In the forebrain of the mutant embryos, severe growth defects and absence of optic vesicles could involve loss of expression of fibroblast growth factor-8, in addition to Shh. Our results also suggest that interaction between gsc and HNF-3β regulates other signalling molecules required for proper development of the foregut, branchial arches and heart.
Genetic separation of the neural and cuticular patterning functions of gooseberry
Authors: Duman-Scheel Molly , Li Xuelin , Orlov Irena , Noll Markus , Patel Nipam H. 
Published: April 2021

ABSTRACT
In addition to their role in the specification of the epidermal pattern in each segment, several segment polarity genes, including gooseberry (gsb), specify cell fate in the Drosophila central nervous system (CNS). Analyses of the gsb CNS phenotype have been complicated by the fact that the previously available gsb mutants, all caused by cyto-logically visible deficiencies, have severe segmentation defects and also lack a number of additional genes. We have characterized two novel gsb mutants which, due to their hypomorphic nature, have CNS defects, but have only weak or no segmentation defects. These gsb alleles, as well as gsb rescue experiments, have allowed us to determine which aspects of the deficiency mutant phenotypes can be attrib-uted to loss of gsb. gsb mutants lack U and CQ neurons, have duplicated RP2 neurons, and display posterior com-missure defects. gsb neural defects, as well as the gsb cuticle defect, are differentially sensitive to the level of functional Gsb. We have used one of the novel gsb alleles in order to understand the genetic interactions between gsb, wingless (wg), and patched (ptc) during the patterning of the ventral neuroectoderm. In contrast to epidermal patterning, where Gsb is required to maintain wg transcription, we find that Gsb antagonizes the Wg signal that confers neuroblast (NB) 4–2 fate.
Hepatocyte growth factor (HGF/SF) is a muscle-derived survival factor for a subpopulation of embryonic motoneurons
Authors: Yamamoto Yoichi , Livet Jean , Pollock Richard A. , Garces Alain , Arce Vilma , deLapeyrière Odile , Henderson Christopher E. 
Published: April 2021

ABSTRACT
Muscle-derived factors are known to be important for the survival of developing spinal motoneurons, but the molecules involved have not been characterized. Hepatocyte growth factor/scatter factor (HGF/SF) plays an important role in muscle development and motoneuron axon outgrowth. We show that HGF/SF has potent neurotrophic activity (EC50=2 pM) for a subpopulation (40%) of purified embryonic rat motoneurons. Moreover, HGF/SF is an essential component of muscle-derived support for motoneurons, since blocking antibodies to HGF/SF specifically inhibited 65% of the trophic activity of media conditioned by C2/C7 skeletal myotubes, but did not inhibit the trophic activity secreted by Schwann cell lines. High levels of expression of the HGF/SF receptor c-Met in the spinal cord are restricted to subsets of motoneurons, mainly in limb-innervating segments. Consistent with this distribution, cultured motoneurons from limb-innervating brachial and lumbar segments showed a more potent response to HGF/SF than did thoracic motoneurons. By the end of the period of motoneuron cell death, levels of c-Met mRNA in motoneurons were markedly reduced, suggesting that the effects of HGF/SF may be limited to the period of motoneuron cell death. HGF/SF may play an important role during motoneuron development as a muscle-derived survival factor for a subpopulation of limb-innervating motoneurons.
Lhx2, a LIM homeobox gene, is required for eye, forebrain, and definitive erythrocyte development
Authors: Porter Forbes D. , Drago John , Xu Yang , Cheema Surindar S. , Wassif Chris , Huang Sing-Ping , Lee Eric , Grinberg Alexander , Massalas Jim S. , Bodine David , Alt Frederick , Westphal Heiner 
Published: April 2021

ABSTRACT
We investigated the function of Lhx2, a LIM homeobox gene expressed in developing B-cells, forebrain and neural retina, by analyzing embryos deficient in functional Lhx2 protein. Lhx2 mutant embryos are anophthalmic, have malformations of the cerebral cortex, and die in utero due to severe anemia. In Lhx2−/− embryos specification of the optic vesicle occurs; however, development of the eye arrests prior to formation of an optic cup. Deficient cellular proliferation in the forebrain results in hypoplasia of the neocortex and aplasia of the hippocampal anlagen. In addition to the central nervous system malformations, a cell non-autonomous defect of definitive erythropoiesis causes severe anemia in Lhx2−/− embryos. Thus Lhx2 is necessary for normal development of the eye, cerebral cortex, and efficient definitive erythropoiesis.
Nanos and pumilio establish embryonic polarity in Drosophila by promoting posterior deadenylation of hunchback mRNA
Authors: Wreden Christopher , Verrotti Arturo C. , Schisa Jennifer A. , Lieberfarb Marshal E. , Strickland Sidney 
Published: April 2021

ABSTRACT
Nanos protein promotes abdominal structures in Drosophila embryos by repressing the translation of maternal hunchback mRNA in the posterior. To study the mechanism of nanos-mediated translational repression, we first examined the mechanism by which maternal hunchback mRNA is translationally activated. In the absence of nanos activity, the poly(A) tail of hunchback mRNA is elongated concomitant with its translation, suggesting that cyto-plasmic polyadenylation directs activation. However, in the presence of nanos the length of the hunchback mRNA poly(A) tail is reduced. To determine if nanos activity represses translation by altering the polyadenylation state of hunchback mRNA, we injected various in vitro transcribed RNAs into Drosophila embryos and determined changes in polyadenylation. Nanos activity reduced the polyadenylation status of injected hunchback RNAs by accelerating their deadenylation. Pumilio activity, which is necessary to repress the translation of hunchback, is also needed to alter polyadenylation. An examination of translation indicates a strong correlation between poly(A) shortening and suppression of translation. These data indicate that nanos and pumilio determine posterior morphology by promoting the deadenylation of maternal hunchback mRNA, thereby repressing its translation.
Mouse-chick chimera: a developmental model of murine neurogenic cells
Authors: Fontaine-Pérus Josiane , Halgand Philippe , Chéraud Yvonnick , Rouaud Thierry , Velasco Maria Elena , Diaz Carmen Cifuentes , Rieger François 
Published: April 2021

ABSTRACT
Chimeras were prepared by transplanting fragments of neural primordium from 8- to 8.5- and 9-day postcoital mouse embryos into 1.5- and 2-day-old chick embryos at different axial levels. Mouse neuroepithelial cells differentiated in ovo and organized to form the different cellular compartments normally constituting the central nervous system. The graft also entered into the development of the peripheral nervous system through migration of neural crest cells associated with mouse neuroepithelium. Depending on the graft level, mouse crest cells participated in the formation of various derivatives such as head components, sensory ganglia, orthosympathetic ganglionic chain, nerves and neuroendocrine glands. Tenascin knockout mice, which express lacZ instead of tenascin and show no tenascin production (Saga, Y., Yagi, J., Ikawa, Y., Sakakura, T. and Aizawa, S. (1992) Genes and Development 6, 1821-1838), were specifically used to label Schwann cells lining nerves derived from the implant. Although our experiments do not consider how mouse neural tube can participate in the mechanism required to maintain myogenesis in the host somites, they show that the grafted neural tube behaves in the same manner as the chick host neural tube. Together with our previous results on somite development (Fontaine-Pérus, J., Jarno, V., Fournier Le Ray, C., Li, Z. and Paulin, D. (1995) Development 121, 1705-1718), this study shows that chick embryo constitutes a privileged environment, facilitating access to the developmental potentials of normal or defective mammalian cells. It allows the study of the histogenesis and precise timing of a known structure, as well as the implication of a given gene at all equivalent mammalian embryonic stages.
Loss-of-function mutations in the maize homeobox gene, knotted1, are defective in shoot meristem maintenance
Authors: Kerstetter Randall A. , Laudencia-Chingcuanco Debbie , Smith Laurie G. , Hake Sarah 
Published: April 2021

ABSTRACT
The product of the maize homeobox gene, knotted1 (kn1), localizes to the nuclei of cells in shoot meristems, but is absent from portions of the meristem where leaf primordia or floral organs initiate. Recessive mutant alleles of kn1 were obtained by screening for loss of the dominant leaf phenotype in maize. Mutant kn1 alleles carrying nonsense, splicing and frame shift mutations cause severe inflorescence and floral defects. Mutant tassels produce fewer branches and spikelets. Ears are often absent, and when present, are small with few spikelets. In addition, extra carpels form in female florets and ovule tissue proliferates abnormally. Less frequently, extra leaves form in the axils of vegetative leaves. These mutations reveal a role for kn1 in meristem maintenance, particularly as it affects branching and lateral organ formation.
Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila
Authors: Haerry Theodor E. , Heslip Tim R. , Marsh J. Lawrence , O’Connor Michael B. 
Published: April 2021

ABSTRACT
In vitro experiments suggest that glycosaminoglycans (GAGs) and the proteins to which they are attached (proteoglycans) are important for modulating growth factor signaling. However, in vivo evidence to support this view has been lacking, in part because mutations that disrupt the production of GAG polymers and the core proteins have not been available. Here we describe the identification and characterization of Drosophila mutants in the suppenkasper (ska) gene. The ska gene encodes UDP-glucose dehydrogenase which produces glucuronic acid, an essential component for the synthesis of heparan and chondroitin sulfate. ska mutants fail to put heparan side chains on proteoglycans such as Syndecan. Surprisingly, mutant embryos produced by germ-line clones of this general metabolic gene exhibit embryonic cuticle phenotypes strikingly similar to those that result from loss-of-function mutations in genes of the Wingless (Wg) signaling pathway. Zygotic loss of ska leads to reduced growth of imaginal discs and pattern defects similar to wg mutants. In addition, genetic interactions of ska with wg and dishevelled mutants are observed. These data demonstrate the importance of proteoglycans and GAGs in Wg signaling in vivo and suggest that Wnt-like growth factors may be particularly sensitive to perturbations of GAG biosynthesis.
Early- and late-migrating cranial neural crest cell populations have equivalent developmental potential in vivo
Authors: Baker Clare V. H. , Bronner-Fraser Marianne , Douarin Nicole M. Le , Teillet Marie-Aimée 
Published: April 2021

ABSTRACT
We present the first in vivo study of the long-term fate and potential of early-migrating and late-migrating mesencephalic neural crest cell populations, by performing isochronic and heterochronic quail-to-chick grafts. Both early- and late-migrating populations form melanocytes, neurons, glia, cartilage and bone in isochronic, isotopic chimeras, showing that neither population is lineagerestricted. The early-migrating population distributes both dorsally and ventrally during normal development, while the late-migrating population is confined dorsally and forms much less cartilage and bone. When the latemigrating population is substituted heterochronically for the early-migrating population, it contributes extensively to ventral derivatives such as jaw cartilage and bone. Conversely, when the early-migrating population is substituted heterochronically for the late-migrating population, it no longer contributes to the jaw skeleton and only forms dorsal derivatives. When the late-migrating population is grafted into a late-stage host whose neural crest had previously been ablated, it migrates ventrally into the jaws. Thus, the dorsal fate restriction of the late-migrating mesencephalic neural crest cell population in normal development is due to the presence of earlier-migrating neural crest cells, rather than to any change in the environment or to any intrinsic difference in migratory ability or potential between early- and late-migrating cell populations. These results highlight the plasticity of the neural crest and show that its fate is determined primarily by the environment.
Temporally-regulated retinoic acid depletion produces specific neural crest, ocular and nervous system defects
Authors: Dickman Eileen D. , Thaller Christina , Smith Susan M. 
Published: April 2021

ABSTRACT
Both retinoid receptor null mutants and classic nutritional deficiency studies have demonstrated that retinoids are essential for the normal development of diverse embryonic structures (e.g. eye, heart, nervous system, urogenital tract). Detailed analysis of retinoid-modulated events is hampered by several limitations of these models, including that deficiency or null mutation is present throughout gestation, making it difficult to isolate primary effects, and preventing analysis beyond embryolethality. We developed a mammalian model in which retinoid-dependent events are documented during distinct targeted windows of embryogenesis. This was accomplished through the production of vitamin A-depleted (VAD) female rats maintained on sufficient oral retinoic acid (RA) for growth and fertility. After mating to normal males, these RA-sufficient/VAD females were given oral RA doses which allowed for gestation in an RA-sufficient state; embryogenesis proceeded normally until retinoids were withdrawn dietarily to produce a sudden, acute retinoid deficiency during a selected gestational window. In this trial, final RA doses were administered on E11.5, vehicle at E12.5, and embryos analyzed on E13.5; during this 48 hour window, the last RA dose was metabolized and embryos progressed in a retinoid-deficient state. RA-sufficient embryos were normal. Retinoiddepleted embryos exhibited specific malformations of the face, neural crest, eyes, heart, and nervous system. Some defects were phenocopies of those seen in null mutant mice for RXRα−/−, RXRα−/−/RARα−/−, and RARα−/−/RARγ−/−, confirming that RA transactivation of its nuclear receptors is essential for normal embryogenesis. Other defects were unique to this deficiency model, showing that complete ligand ‘knock-out’ is required to see those retinoiddependent events previously concealed by receptor functional redundancy, and reinforcing that retinoid receptors have separate yet overlapping contributions in the embryo. This model allows for precise targeting of retinoid form and deficiency to specific developmental windows, and will facilitate studies of distinct temporal events.