bluuebunny/crossref_metadata_2025_split huggingface dataset:
The expression of trkB and p75 and the role of BDNF in the developing neuromuscular system of the chick embryo
Authors: McKay S. E. , Garner A. , Caldero J. , Tucker R. P. , Large T. , Oppenheim R. W. 
Published: April 2021

ABSTRACT
The neurotrophin, brain-derived neurotrophic factor, prevents motoneuron cell death during the normal development of the chick embryo. Brain-derived neurotrophic factor is a ligand for the low-affinity NGF receptor, p75, and for the high-affinity neurotrophin receptor, trkB. If motoneurons respond directly to brain-derived neurotrophic factor then they must possess at least one, and possibly both, of these receptors during the period of naturally occurring cell death. Histological sections from the lumbar region of chick embryos were probed for the presence of trkB and p75 mRNA using digoxigenin-labeled anti-sense RNA probes. p75 mRNA was present in spinal cord motoneurons at stages of development that correlate with motoneuron cell death. Immunohistochemical localization also revealed that p75 protein was present in motoneurons, primarily along the ventral roots and developing intramuscular nerves. In contrast, trkB mRNA was not present in chick motoneurons until after the process of cell death was underway. The timing of trkB expression suggested that some motoneurons, i.e., those that die prior to the onset of trkB expression, may be insensitive to brainderived neurotrophic factor. This was confirmed by comparing the number of surviving motoneurons following different in vivo treatment paradigms. The evidence indicates that motoneurons undergo a temporal shift in sensitivity to brain-derived neurotrophic factor.
A Dictyostelium mutant with defective aggregate size determination
Authors: Brock Debra A. , Buczynski Greg , Spann Timothy P. , Wood Salli A. , Cardelli James , Gomer Richard H. 
Published: April 2021

ABSTRACT
Starved Dictyostelium cells aggregate into groups of roughly 105 cells. We have identified a gene which, when repressed by antisense transformation or homologous recombination, causes starved cells to form large numbers of small aggregates. We call the gene smlA for small aggregates. A roughly 1.0 kb smlA mRNA is expressed in vegetative and early developing cells, and the mRNA level then decreases at about 10 hours of development. The sequence of the cDNA and the derived amino acid sequence of the SmlA protein show no significant similarity to any known sequence. There are no obvious motifs in the protein or large regions of hydrophobicity or charge. Immunofluorescence and staining of Western blots of cell fractions indicates that SmlA is a 35×103Mr cytosolic protein present in all vegetative and developing cells and is absent from smlA cells. The absence of SmlA does not affect the growth rate, cell cycle, motility, differentiation, or developmental speed of cells. Synergy experiments indicate that mixing 5% smlA cells with wild-type cells will cause the wild-type cells to form smaller fruiting bodies and aggregates. Although there is no detectable SmlA protein secreted from cells, starvation medium conditioned by smlA cells will cause wild-type cells to form large numbers of small aggregates. The component in the smlA-conditioned media that affects aggregate size is a molecule with a molecular mass greater than 100×103Mr that is not conditioned media factor, phosphodiesterase or the phosphodiesterase inhibitor. The data thus suggest that the cytosolic protein SmlA regulates the secretion or processing of a secreted factor that regulates aggregate size.
Function of posterior HoxD genes in the morphogenesis of the anal sphincter
Authors: Kondo Takashi , Dollé Pascal , Zákány Jozsef , Duboule Denis 
Published: April 2021

ABSTRACT
Vertebrate 5′-located HoxD genes are expressed in the most caudal part of the digestive tract and their potential functions during gut development have been assessed by gene disruptions. We have inserted reporter lacZ sequences within the Hoxd-12 gene and analysed the morphology of the gut in these mice as well as in Hoxd-13 mutant animals. When homozygous, both mutations induce an important disorganization of the anorectal region. In particular, severe alterations of the smooth muscle layers of the rectum led to defective morphogenesis of the internal anal sphincter. Similarly, Hoxd-12 and Hoxd-13 functionally overlap during digit development. The function of these genes in the morphogenesis of the digestive system as well as their functional evolution are discussed.
CSF-1 deficiency in mice results in abnormal brain development
Authors: Michaelson M. Dror , Bieri Phyllis L. , Mehler Mark F. , Xu Hong , Arezzo Joseph C. , Pollard Jeffrey W. , Kessler John A. 
Published: April 2021

ABSTRACT
Colony stimulating factor-1 (CSF-1) was initially identified as a growth factor for mononuclear phagocytes. This study examines the role of CSF-1 in the development of the central nervous system (CNS). CSF-1 treatment of neurons cultured from embryonic brain promoted survival and process outgrowth in a dose-dependent manner. By contrast, CSF-1 treatment of neurons cultured from the osteopetrotic (op/op) mouse, a null mutant for CSF-1, promoted significantly less process outgrowth, suggesting that there are neural abnormalities in op/op animals. Nuclease protection assays were used to determine whether CSF-1 and its receptor are expressed at times appropriate to regulate neural development. Both CSF-1 and its receptor are expressed in developing mouse brain, with a unique pattern of CSF-1 mRNA splice variant expression encoding secreted, and not membrane-bound, growth factor. To determine whether brain function is altered by null mutation of CSF-1, op/op mice were examined using electrophysiologic assays. Brainstem auditory and visual evoked potentials were both abnormal in op/op mice. Further, intracortical recordings revealed aberrant neuronal function within visual cortex and alterations in the cortical circuitry that balances excitation and inhibition. Daily CSF-1 injection of postnatal op/op mice largely rescued the abnormal neural phenotype, confirming that the absence of CSF-1 during development is responsible for the abnormalities. The effects of CSF-1 on cultured embryonic neural cells, the developmentally appropriate expression of CSF-1 and its receptor, and the neurological abnormalities in op/op mice suggest a role for CSF-1 in brain development.
Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression
Authors: Benson Gail V. , Lim Hyunjung , Paria B. C. , Satokata Ichiro , Dey Sudhansu K. , Maas Richard L. 
Published: April 2021

ABSTRACT
The establishment of a receptive uterine environment is critical for embryonic survival and implantation. One gene that is expressed in the uterus during the peri-implantation period in mice and is required for female fertility is the homeobox gene Hoxa-10. Here we characterize the periimplantation defects in Hoxa-10 mutant females and investigate functions of Hoxa-10 in the uterine anlage during morphogenesis and in the adult uterus during pregnancy. Examination of pregnancy in Hoxa-10 mutant females has revealed failure of implantation as well as resorption of embryos in the early postimplantation period. Morphologic analysis of the mutant uterus has demonstrated homeotic transformation of the proximal 25% into oviduct. Histology and molecular markers confirm this anterior transformation. Furthermore, in situ hybridization shows that this region coincides with the anterior limit of embryonic Hoxa-10 expression in the urogenital ducts and a parallel transformation is observed in Hoxa-10 mutant males at the junction of the epididymis and ductus deferens. Female fertility could be compromised by either the homeotic transformation or the absence of Hoxa-10 function in the adult during pregnancy. To distinguish between these two potential mechanisms of infertility, wildtype blastocysts were transferred into mutant uteri distal to the transformed region on day 2.5 of pseudopregnancy. This procedure did not rescue the phenotype, suggesting that adult uterine expression of Hoxa-10 is required during pregnancy. Moreover, when implantation was experimentally delayed, homozygous uteri were able to support survival of blastocysts comparable to wild-type controls, indicating that the requirement for Hoxa-10 is intrinsic to implantation. While expression of LIF and HB-EGF appears unaffected in the mutant uteri, a decrease is observed in the intensity and number of blue dye reactions, an indicator of increased vascular permeability in response to implantation. In addition, mutant uteri exhibited decreased decidualization in response to artificial stimuli. These results show that Hoxa-10 is required during morphogenesis for proper patterning of the reproductive tract and in the adult uterus for peri-implantation events.
Positive and negative signals modulate formation of the Xenopus cement gland
Authors: Bradley Leila , Wainstock Daniel , Sive Hazel 
Published: April 2021

ABSTRACT
The cement gland is a simple secretory organ that marks the anterior-most dorsal ectoderm in Xenopus embryos. In this study, we examine the timing of cement gland induction and the cell interactions that contribute to cement gland formation. Firstly, we show that the outer ectodermal layer, from which the cement gland arises, becomes specified as cement gland by mid-gastrula. Curiously, at early gastrula, the inner layer of the dorsal ectoderm, which does not contribute to the mature cement gland, is strongly and transiently specified as cement gland. Secondly, we show that the mid-gastrula dorsoanterior yolky endoderm, which comes to underlie the cement gland primordium, is a potent inducer of cement gland formation and patterning. The cement gland itself has an anteroposterior pattern, with the gene XA expressed only posteriorly. Dorsoanterior yolky endoderm greatly enhances formation of large, patterned cement glands in partially induced anterodorsal ectoderm, but is unable to induce cement gland in naive animal caps. Neural tissue is induced less frequently than cement gland by the dorsoanterior yolky endoderm, suggesting that the endoderm induces cement gland directly. Thirdly, we demonstrate that the ventral ectoderm adjacent to the cement gland attenuates cement gland differentiation late during gastrulation. The more distant ventral mesendoderm is also a potent inhibitor of cement gland formation. These are the first data showing that normal ventral tissues can inhibit cement gland differentiation and suggest that cement gland size and position may be partly regulated by negative signals. Previous work has shown that cement gland can be induced by neural plate and by dorsal mesoderm. Together, these data suggest that cement gland induction is a complex process regulated by multiple positive and negative cell interactions.
derailed is required for muscle attachment site selection in Drosophila
Authors: Callahan Christopher A. , Bonkovsky Joshua L. , Scully Audra L. , Thomas John B. 
Published: April 2021

ABSTRACT
During development, muscles must form and attach at highly stereotyped positions to allow for coordinated movements. In Drosophila, muscles grow towards and attach to specifically positioned cells within the epidermis. At the molecular level, very little is known about how muscles recognize these attachment sites. The derailed gene encodes a receptor tyrosine kinase family member that is essential for the pathfinding ability of expressing neurons. Here we show that the Drl RTK is also expressed by a small subset of developing embryonic muscles and neighboring epidermal cells during muscle attachment site selection. In drl mutants, these muscles often fail to attach at appropriate locations although their epidermal attachment cells appear unaffected. These results show that, similar to its role in neuronal pathway recognition, the Drl RTK participates in a mechanism required for muscle attachment site selection. The data suggest that both neurons and muscles use common mechanisms to recognize their paths or targets, and that Drl plays an analogous role in both developing systems.
A male-specific role for SOX9 in vertebrate sex determination
Authors: Kent Jill , Wheatley Susan C. , Andrews Jane E. , Sinclair Andrew H. , Koopman Peter 
Published: April 2021

ABSTRACT
Mutation analyses of patients with campomelic dysplasia, a bone dysmorphology and XY sex reversal syndrome, indicate that the SRY-related gene SOX9 is involved in both skeletal development and sex determination. To clarify the role SOX9 plays in vertebrate sex determination, we have investigated its expression during gonad development in mouse and chicken embryos. In the mouse, high levels of Sox9 mRNA were found in male (XY) but not female (XX) genital ridges, and were localised to the sex cords of the developing testis. Purified fetal germ cells lacked Sox9 expression, indicating that Sox9 expression is specific to the Sertoli cell lineage. Sex specificity of SOX9 protein expression was confirmed using a polyclonal antiserum. The timing and cell-type specificity of Sox9 expression suggests that Sox9 may be directly regulated by SRY. Male-specific expression of cSOX9 mRNA during the sex determination period was also observed in chicken genital ridges. The conservation of sexually dimorphic expression in two vertebrate classes which have significant differences in their sex determination mechanisms, points to a fundamental role for SOX9 in testis determination in vertebrates.
Sox9 expression was maintained in the mouse testis during fetal and adult life, but no expression was seen at any stage by in situ hybridisation in the developing ovary. Male-specific expression was also observed in the cells surrounding the Müllerian ducts and in the epididymis, and expression in both sexes was detected in the developing collecting ducts of the metanephric kidney. These results suggest that SOX9 may have a wider role in the development of the genitourinary system.
A Ras-mediated signal transduction pathway is involved in the control of sex myoblast migration in Caenorhabditis elegans
Authors: Sundaram Meera , Yochem John , Han Min 
Published: April 2021

ABSTRACT
Sex myoblast migration in the Caenorhabditis elegans hermaphrodite represents a simple, genetically amenable model system for studying how cell migration is regulated during development. Two separable components of sex myoblast guidance have been described: a gonad-independent mechanism sufficient for the initial anterior migration to the mid-body region, and a gonad-dependent mechanism required for precise final positioning (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041-1052). Here, we demonstrate a role for a Ras-mediated signal transduction pathway in controlling sex myoblast migration. Lossof-function mutations in let-60 ras, ksr-1, lin-45 raf, let537/mek-2 or sur-1/mpk-1 cause defects in sex myoblast final positions that resemble those seen in gonad-ablated animals, while constitutively active let-60 ras(G13E) transgenes allow fairly precise positioning to occur in the absence of the gonad. A mosaic analysis demonstrated that let-60 ras is required within the sex myoblasts to control proper positioning. Our results suggest that gonadal signals normally stimulate let-60 ras activity in the sex myoblasts, thereby making them competent to sense or respond to positional cues that determine the precise endpoint of migration. let-60 ras may have additional roles in sex myoblast guidance as well. Finally, we have also investigated genetic interactions between let-60 ras and other genes important for sex myoblast migration, including egl15, which encodes a fibroblast growth factor receptor tyrosine kinase (D. L. DeVore, H. R. Horvitz and M. J. Stern (1995) Cell 83, 611-623). Since mutations reducing Ras pathway activity cause a different phenotype than those reducing egl-15 activity and since constitutive Ras activity only partially suppresses the migration defects of egl-15 mutants, we argue that let-60 ras and egl-15 do not act together in a single linear pathway.
The patched signaling pathway mediates repression of gooseberry allowing neuroblast specification by wingless during Drosophila neurogenesis
Authors: Bhat Krishna Moorthi 
Published: April 2021

ABSTRACT
The Drosophila signaling molecule Wingless (Wg) plays crucial roles in cell-cell communications during development. In the developing nervous system, a previous study has shown that Wg acts non-autonomously to specify the fate of a specific neuronal precursor, NB4-2 (Q. ChuLaGraff and C. Q. Doe (1993) Science 261, 1594-1597). The lack of autocrine specification of NB4-2 in Wg-expressing cells suggests that the response to Wg is spatially restricted, presumably through the activity of the Wg-receptor. I show that two other proteins, a transcription factor Gooseberry (Gsb) and a transmembrane protein Patched (Ptc), participate in the Wg-mediated specification of NB4-2 by controlling the response to the Wg signal. In gsb mutants, Wgpositive NB5-3 is transformed to NB4-2 in a Wg-dependent manner, suggesting that Gsb normally represses the capacity to respond to the Wg signal. In ptc mutants, Gsb is ectopically expressed in normally Wg-responsive cells, thus preventing the Wg response and consequently the correct specification of NB4-2 does not take place. This conclusion is supported by the observation that NB4-2 can be specified in gsb;ptc double mutants in a Wg-dependent manner. Moreover, ectopic expression of Gsb from the hsp70-gsb transgene also blocks the response to the Wg signal. I propose that the responsiveness to the Wg signal is controlled by sequential negative regulation, ptc→gsb→Wg receptor. The timing of the response to Gsb suggests that the specification of neuroblast identities takes place within the neuroectoderm, prior to neuroblast delamination.
Localization of Xcat-2 RNA, a putative germ plasm component, to the mitochondrial cloud in Xenopus stage I oocytes
Authors: Zhou Yi , King Mary Lou 
Published: April 2021

ABSTRACT
The mitochondrial cloud is a unique cell structure found in stage I Xenopus oocytes that plays a role in mitochondriogenesis and in the distribution of germ plasm to the vegetal pole. Xcat-2 RNA specifically localizes to the mitochondrial cloud and moves with it to the vegetal subcortex in stage II oocytes. Later, in the 4-cell embryo, it is found in a pattern identical to the germ plasm. Following microinjection into stage I oocytes, synthetic Xcat-2 RNAs localize to the mitochondrial cloud within 22 hours. Transcripts are stable over this time period with very little evidence of degradation. The Xcat-2 3′untranslated region was found to be both required and sufficient for mitochondrial cloud localization. Further deletion analysis narrowed this localization signal to a 250 nucleotide region at the proximal end of the 3′untranslated region. This region is different from, but overlaps with, a domain previously shown to be sufficient to direct Xcat-2 to the vegetal cortex in stage IV oocytes. Examination of early stage I oocytes reveals a time when Xcat-2 is uniformly distributed, arguing against vectorial nuclear export into the mitochondrial cloud. Analysis of localization at different time points does not suggest active transport to the mitochondrial cloud. We postulate that localization occurs by selective entrapment of Xcat-2 within the cloud by localized binding sites.
The hardwiring of development: organization and function of genomic regulatory systems
Authors: Arnone Maria I. , Davidson Eric H. 
Published: April 2021

ABSTRACT
The gene regulatory apparatus that directs development is encoded in the DNA, in the form of organized arrays of transcription factor target sites. Genes are regulated by interactions with multiple transcription factors and the target sites for the transcription factors required for the control of each gene constitute its cis-regulatory system. These systems are remarkably complex. Their hardwired internal organization enables them to behave as genomic information processing systems. Developmental gene regulatory networks consist of the cis-regulatory systems of all the relevant genes and the regulatory linkages amongst them. Though there is yet little explicit information, some general properties of genomic regulatory networks have become apparent. The key to understanding how genomic regulatory networks are organized, and how they work, lies in experimental analysis of cis-regulatory systems at all levels of the regulatory network.
Skeletal morphogenesis in the sea urchin embryo: regulation of primary mesenchyme gene expression and skeletal rod growth by ectoderm-derived cues
Authors: Guss Kirsten A. , Ettensohn Charles A. 
Published: April 2021

ABSTRACT
The skeleton of the sea urchin embryo is synthesized by the primary mesenchyme cells (PMCs). Previous studies have shown that local interactions between PMCs and the neighboring ectoderm regulate several aspects of skeletal morphogenesis, including PMC distribution in the blastocoel, the size of the skeleton and its branching pattern. In the present study, we have further examined the regulation of skeletogenesis by the ectoderm. We generated a ‘rate map’ of skeletal growth, which revealed stereotypical changes in the rates at which specific skeletal elements elongate during development. We showed that three transcripts encoding PMC-specific gene products known to be involved in the synthesis of the skeleton exhibited dynamic, spatially regulated patterns of expression within the PMC syncytium. All three gene products showed high levels of expression at sites of skeletal rod growth, although the specific patterns varied among the genes. We present direct evidence, based upon cell transplantation experiments, that the expression of one of these genes,SM30, is responsive to local, ectoderm-derived cues. Based upon our studies, we suggest that short-range signals from different ectodermal territories may regulate the expression of PMC-specific gene products that are rate-limiting in skeletal biosynthesis, thereby locally influencing skeletal rod growth.
Identification of a lineage of multipotent hematopoietic progenitors
Authors: Morrison Sean J. , Wandycz Antoni M. , Hemmati Houman D. , Wright Douglas E. , Weissman Irving L. 
Published: April 2021

ABSTRACT
All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1loSca-1+Lin−/loc-kit+cells:long-term reconstituting Mac-1−CD4−c-kit+ cells and transiently reconstituting Mac-1loCD4− or Mac-1loCD4lo cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1−CD4−c-kit+ cells gave rise to Mac-1loCD4− cells, which gave rise to Mac-1loCD4lo cells. Mac-1−CD4−c-kit+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 104 functionally similar Mac-1−CD4−c-kit+ cells. At least half of Mac-1loCD4− cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1loCD4lo cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment.