bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABAergic stimulation switches from enhancing to repressing BDNF expression in rat hippocampal neurons during maturation in vitro
Authors: Berninger Benedikt , Marty Serge , Zafra Francisco , Berzaghi Maria da Penha , Thoenen Hans , Lindholm Dan 
Published: April 2021

ABSTRACT
γ-aminobutyric acid (GABA) is the major inhibitory neu-rotransmitter in the adult mammalian central nervous system. However, GABA depolarizes immature rat hip-pocampal neurons and increases intracellular Ca2+ ([Ca2+]i). Here we show, that GABA and the GABAA receptor agonist muscimol induce c-Fos immunoreactivity and increase BDNF mRNA expression in embryonic hip-pocampal neurons cultured for 5 days. In contrast, after 3 weeks in culture, GABA and muscimol failed to induce c-fos and BDNF expression. Fura-2 fluorescence microscopy revealed that muscimol produces a dihydropyridine-sensitive transient increase in [Ca2+]i, comparable to the effect of the non-NMDA receptor agonist kainic acid in neurons cultured for 5 days, but not in 3-week-old cultures. The increase in c-Fos immunoreactivity and BDNF mRNA levels by GABA were dependent upon the activation of voltage-gated Ca2+ channels, as shown using the L-type specific Ca2+ channel blocker nifedipine. The differential regulation of c-fos and BDNF expression by GABA and muscimol in developing and mature hippocampal neurons is due to a switch in the ability of GABAA receptors to activate voltage-gated Ca2+ channels. These observations support the hypothesis that GABA might have neurotrophic effects on embryonic or perinatal hippocampal neurons, which are mediated by BDNF.
Multiple mechanisms regulate sympathetic neuronal phenotype
Authors: Hall Alison K. , MacPhedran Sally E. 
Published: April 2021

ABSTRACT
Adult rat sympathetic neurons can possess specific neuropeptides utilized as cotransmitters along with norepinephrine, but the factors that regulate their expression remain unknown. 60% of adult rat superior cervical ganglion (SCG) neurons express neuropeptide Y (NPY) in vivo. To determine whether the restricted expression was an intrinsic property of sympathetic ganglia, we examined if embryonic sympathetic precursors gave rise to NPY immunoreactive (-IR) neurons in vitro. After one week in culture, 60% of neurons derived from the E14.5 rat SCG were NPY-IR. Thus, ganglia isolated before peripheral target contact or preganglionic innervation were capable of regulating NPY expression both in the number of neurons with NPY and in the developmental timing of NPY expression. To determine if the restricted expression of NPY was a reflection of neuroblasts committed to an NPY fate, SCG precursors were labeled with a replication incompetent retrovirus carrying lacZ, and NPY expression in lacZ-labeled clones examined after one week. Two thirds of neuronal clones obtained were uniformly NPY-IR; that is, all neurons in a clone either possessed or lacked NPY. One-third of the neuronal clones were mixed and contained both neurons with and without NPY. We provide a novel demonstration that both lineage and environmental cues contribute to neuropeptide phenotype.
The induction of multiple cell cycle events precedes target-related neuronal death
Authors: Herrup Karl , Busser Jonathan C. 
Published: April 2021

ABSTRACT
Unexpected nerve cell death has been reported in several experimental situations where neurons have been forced to re-enter the cell cycle after leaving the ventricular zone and entering the G0, non-mitotic stage. To determine whether an association between cell death and unscheduled cell cycling might be found in conjunction with any naturally occurring developmental events, we have examined target-related cell death in two neuronal populations, the granule cells of the cerebellar cortex and the neurons of the inferior olive. Both of these cell populations have a demonstrated developmental dependency on their synaptic target, the cerebellar Purkinje cell. Two mouse neurological mutants, staggerer (sg/sg) and lurcher (+/Lc), are characterized by intrinsic Purkinje cell deficiencies and, in both mutants, substantial numbers of cerebellar granule cells and inferior olive neurons die due to the absence of trophic support from their main postsynaptic target. We report here that the levels of three independent cell cycle markers – cyclin D, proliferating cell nuclear antigen and bromodeoxyuridine incorporation – are elevated in the granule cells before they die. Although lurcher Purkinje cells die during a similar developmental period, no compelling evidence for any cell cycle involvement in this instance of pre-programmed cell death could be found. While application of the TUNEL technique (in situ terminal transferase end-labeling of fragmented DNA) failed to label dying granule cells in either mutant, light and electron microscopic observations are consistent with the interpretation that the death of these cells is apoptotic in nature. Together, the data indicate that target-related cell death in the developing central nervous system is associated with a mechanism of cell death that involves an apparent loss of cell cycle control.
PDGF-AA and its receptor influence early lung branching via an epithelial–mesenchymal interaction
Authors: Souza Patricia , Kuliszewski Maciej , Wang Jinxia , Tseu Irene , Tanswell A. Keith , Post Martin 
Published: April 2021

ABSTRACT
The biological role of platelet-derived growth factor (PDGF)-AA in lung morphogenesis was investigated by incubating embryonic lung explants with phosphorothioate antisense PDGF-A oligonucleotides, which decreased PDGF-AA but not PDGF-BB protein content. Antisense PDGF-A oligonucleotides inhibited DNA synthesis. This inhibitory effect of antisense PDGF-A was reversed by the addition of exogenous PDGF-AA but not PDGF-BB. Morphometric analyses of antisense-treated cultures showed a significant reduction in lung size. The number of terminal buds of the lung explants was significantly decreased by antisense PDGF-A oligonucleotides. PDGF-AA but not PDGF-BB attenuated the inhibitory effect of antisense PDGF-A on early lung branching. Sense PDGF-A had no effect on DNA synthesis and early lung branching. Reverse transcriptase-polymerase chain reaction analysis revealed PDGF-A mRNA expression in the epithelial component of the embryonic lung, while message for PDGF α-receptor was expressed in the mesenchyme. Incubation of explants with neutralizing PDGF-AA antibodies also reduced DNA synthesis and early branching morphogenesis. We conclude that PDGF-AA and its receptor represent an important epithelial-mesenchymal interaction which plays a critical role in early lung branching morphogenesis.
Absence of topography in precociously innervated tecta
Authors: Chien Chi-Bin , Cornel Elsa M. , Holt Christine E. 
Published: April 2021

ABSTRACT
The retinotectal map in Xenopus forms very early: retinal axons are topographically ordered along the dorsoventral axis of the tectum by stage 39, as they first arrive. To test whether topographic cues are present even earlier, we forced retinal axons to innervate the tectum prematurely by transplanting stage 28 eye primordia into stage 20 hosts, then assayed dorsoventral topography using focal injections of lipophilic dye into dorsal and ventral retina at donor stages 39-40. Unoperated and isochronic control projections showed normal dorsoventral ordering both in the optic tract and in the tectum. In contrast, projections from heterochronically transplanted eyes were ordered in the tract, but spread out upon entering the tectum and did not show significant dorsoventral ordering. Individual axons entering the tectum precociously often made abnormally abrupt and topographically incorrect turns. Thus, the topographical cues normally expressed in the tectum at stage 39 appear to be absent a few hours earlier. However, this lack of cues is only temporary, since heterochronic transplants allowed to survive to donor stages 45-46 showed normal topography. The absence of tectal topography at a stage when retinal axons can navigate to the young tectum strongly suggests that the molecules that provide tectal topographical signals are distinct from those used for pathfinding in the diencephalon and target recognition at the tectum.
Deltex acts as a positive regulator of Notch signaling through interactions with the Notch ankyrin repeats
Authors: Matsuno Kenji , Diederich Robert J. , Go Masahiro J. , Blaumueller Christine M. , Artavanis-Tsakonas Spyros 
Published: April 2021

ABSTRACT
We present a molecular and genetic analysis which elucidates the role of deltex in the Notch signaling pathway. Using the yeast ‘interaction trap’ assay, we define the protein regions responsible for heterotypic interactions between Deltex and the intracellular domain of Notch as well as uncover homotypic interaction among Deltex molecules. The function of the Deltex-Notch interaction domains is examined by in vivo expression studies. Taken together, data from overexpression of Deltex fragments and from studies of physical interactions between Deltex and Notch, suggest that Deltex positively regulates the Notch pathway through interactions with the Notch ankyrin repeats. Experiments involving cell cultures indicate that the Deltex-Notch interaction prevents the cytoplasmic retention of the Suppressor of Hairless protein, which otherwise is sequestered in the cytoplasm via association with the Notch ankyrin repeats and translocates to the nucleus when Notch binds to its ligand Delta. On the basis of these findings, we propose a model wherein Deltex regulates Notch activity by antagonizing the interaction between Notch and Suppressor of Hairless.
Properties of the dorsal activity found in the vegetal cortical cytoplasm of Xenopus eggs
Authors: Holowacz Tamara , Elinson Richard P. 
Published: April 2021

ABSTRACT
The Xenopus egg contains a maternal dorsal determinant that is specifically localized to the vegetal cortex. We have previously shown that vegetal cortical cytoplasm can generate a full dorsal axis when it is injected into ventral vegetal blastomeres of a cleavage-stage embryo. In this study, we have defined further the properties of the dorsal activity. The cortical dorsal activity arises during oocyte maturation after germinal vesicle breakdown. When injected into the four extreme animal pole blastomeres of ultraviolet-ventralized 32-cell embryos, vegetal cortical cytoplasm partially rescued dorsal axial structures. As revealed by lineage tracing, these axial structures formed ectopically from the progeny of the cells that were injected. Injection of animal cortical cytoplasm had no effect. When mid-blastula (stage 8) animal caps from these injected embryos were isolated and cultured, both vegetal cortexenriched and animal cortex-enriched animal caps produced only epidermis. Therefore vegetal cortex, on its own, is not a mesoderm inducer. Between stage 8 (blastula) and stage 10 (gastrula), a ventral mesoderm-inducing signal spreads from vegetal cells towards the animal pole. We tested whether this natural mesoderm-inducing factor interacts with the activity found in the vegetal cortex. Injection of vegetal cortex enhanced the formation of neural tissue and cement gland when animal caps were isolated at stage 10. When cultured from stage 8 in the presence of the ventral mesoderm-inducing fibroblast growth factor, animal caps enriched in vegetal cortex developed significantly more neural tissue and cement gland than ones enriched in animal cortex. These results indicate that the dorsal activity localized to the egg vegetal cortex alters the response of cells to mesoderm inducers.
Notch regulates wingless expression and is not required for reception of the paracrine wingless signal during wing margin neurogenesis in Drosophila
Authors: Rulifson Eric J. , Blair Seth S. 
Published: April 2021

ABSTRACT
In the developing wing margin of Drosophila, wingless is normally expressed in a narrow stripe of cells adjacent to the proneural cells that form the sensory bristles of the margin. Previous work has shown that this wingless is required for the expression of the proneural achaete-scute complex genes and the subsequent formation of the sensory bristles along the margin; recently, it has been proposed that the proneural cells require the Notch protein to properly receive the wingless signal. We have used clonal analysis of a null allele of Notch to test this idea directly. We found that Notch was not required by prospective proneural margin cells for the expression of scute or the formation of sensory precursors, indicating Notch is not required for the reception of wingless signal. Loss of Notch from proneural cells produced cell-autonomous neurogenic phenotypes and precocious differentiation of sensory cells, as would be expected if Notch had a role in lateral inhibition within the proneural regions. However, loss of scute expression and of sensory precursors was observed if clones substantially included the normal region of wingless expression. These ‘anti-proneural’ phenotypes were associated with the loss of wingless expression; this loss may be partially or wholly responsible for the anti-proneural phenotype. Curiously, Notch− clones limited to the dorsal or ventral compartments could disrupt wingless expression and proneural development in the adjacent compartment. Analysis using the temperature-sensitive Notch allele indicated that the role of Notch in the regulation of wingless expression precedes the requirement for lateral inhibition in proneural cells. Furthermore, overexpression of wingless with a heat shock-wingless construct rescued the loss of sensory precursors associated with the early loss of Notch.
shortsighted acts in the decapentaplegic pathway in Drosophila eye development and has homology to a mouse TGF-β-responsive gene
Authors: Treisman Jessica E. , Lai Zhi-Chun , Rubin Gerald M. 
Published: April 2021

ABSTRACT
Differentiation in the Drosophila eye imaginal disc traverses the disc as a wave moving from posterior to anterior. The propagation of this wave is driven by hedgehog protein secreted by the differentiated cells in the posterior region of the disc. Hedgehog induces decapentaplegic expression at the front of differentiation, in the morphogenetic furrow. We have identified a gene, shortsighted, which is expressed in a hedgehog-dependent stripe in the undifferentiated cells just anterior to the furrow and which appears to be involved in the transmission of the differentiation-inducing signal; a reduction in shortsighted function leads to a delay in differentiation and to a loss of photoreceptors in the adult. shortsighted is also required for a morphogenetic movement in the brain that reorients the second optic lobe relative to the first. shortsighted encodes a cytoplasmic leucine zipper protein with homology to a mouse gene, TSC-22, which is transcriptionally induced in response to TGF-β.
Genetic ablation of petal and stamen primordia to elucidate cell interactions during floral development
Authors: Day Christopher D. , Galgoci Bernard F. C. , Irish Vivian F. 
Published: April 2021

ABSTRACT
Two models have been proposed to explain the coordinated development of the four whorls of floral organs. The spatial model predicts that positional information defines the four whorls simultaneously, and that individual organs develop independently of surrounding tissues. The sequential model suggests that inductive events between the outer and inner whorl primordia are required for appropriate organogenesis. To test these models we have genetically ablated second and third whorl floral organ primordia to determine if organ identity, number or position are perturbed in the first or fourth whorls. We used diphtheria toxin to specifically ablate floral cells early in development in Nicotiana tabacum and in Arabidopsis thaliana. Second and third whorl expression of the diphtheria toxin A chain coding sequence (DTA) was conferred by the Arabidopsis APETALA3 (AP3) promoter. Both Nicotiana and Arabidopsis flowers that express the AP3-DTA construct lack petals and stamens; it appears that the second and third whorl cells expressing this construct arrest early in floral development. These results show that first and fourth whorl development is normal and can proceed without information from adjacent second and third whorl primordia. We propose that positional information specifies the establishment of all four whorls of organs prior to the expression of AP3 in the floral meristem.
HGF/SF: a potent cytokine for mammary growth, morphogenesis and development
Authors: Niranjan Birunthi , Buluwela Lakjaya , Yant Jeffrey , Perusinghe Nina , Atherton Amanda , Phippard Deborah , Dale Trevor , Gusterson Barry , Kamalati Tahereh 
Published: April 2021

ABSTRACT
The mammary gland is a renewing tissue in which morphogenetic processes and differentiation occur cyclically during the menstrual cycle, pregnancy and lactation. These events have been shown to be dependent upon epithelial-mesenchymal interactions. Studies of the effects of individual factors, their cellular source and their target cell populations in the different developmental stages of the mammary gland are greatly facilitated by the accessibility of this organ and the application of new techniques that allow purification of the major epithelial and stromal components of this tissue.
Here we demonstrate that HGF/SF and its cellular receptor, c-met, are expressed and regulated temporally during mouse mammary development and differentiation. We show that human and mouse mammary fibroblasts produce HGF/SF and that HGF/SF is not only mitogenic but morphogenic and motogenic for both human and mouse mammary epithelial cells. We have found that human luminal and myoepithelial cells express c-met differentially and that HGF/SF has different effects on these two mammary epithelial cell populations. HGF/SF is mitogenic for luminal cells but not myoepithelial cells, and morphogenic to myoepithelial cells but not luminal cells. This is discussed in the context of the proliferative compartments in the normal mammary gland and the potential role of the myoepithelial cells to act as the skeleton for ductal development.
Gratuitous mRNA localization in the Drosophila oocyte
Authors: Serano Thomas L. , Cohen Robert S. 
Published: April 2021

ABSTRACT
Many of the genes that control pattern formation in Drosophila encode mRNAs that are localized to discrete regions of the oocyte during oogenesis. While such localization is generally assumed to be important for the pattern-forming activities of these genes, this has been rigorously demonstrated in only a few cases. Here we address the role of mRNA localization for the dorsoventral patterning gene K10. K10 mRNA is localized to the oocyte’s anterior cortex following its transport into the cell during early stages of oogenesis. We show that mutations in cappuccino and spire, which permit K10 mRNA transport, but prevent subsequent anterior localization, do not disrupt the synthesis or localization of K10 protein. We also show that modified K10 transgenes that produce transcripts which are uniformly distributed throughout the oocyte, or which are mislocalized to the oocyte’s posterior pole, produce localized and functional K10 protein. We conclude that the anterior localization of K10 mRNA is not important for K10 protein targeting or gene function. We propose that the anterior localization of K10, and probably other mRNAs, is a by-product of mRNA transport and does not necessarily reflect a requirement for localization per see.
Sex-specific differentiation of a male-specific abdominal muscle, the Muscle of Lawrence, is abnormal in hydroxyurea-treated and in fruitless male flies
Authors: Taylor Barbara J. , Knittel Laura M. 
Published: April 2021

ABSTRACT
A prominent sex-specific abdominal muscle in male Drosophila is the Muscle of Lawrence (MOL), which is induced by male-specific innervation. We have examined MOL development in wild-type males, in males fed hydroxyurea to ablate the muscle precursors and in fruitless mutants, in which the MOL muscle develops aberrantly. One striking feature of MOLs in wild-type males was the presence of additional muscle nuclei compared with neighboring muscles or MOL-homologues in females. We tested whether muscle length and the sex-specific expression of a reporter gene depended critically on the number of nuclei present within a MOL fiber. MOL fibers developing from a reduced myoblast pool in hydroxyurea-affected hemisegments were recognizable by their attachment points and still contained more nuclei than did neighboring medial fibers, suggesting that these MOL fibers were able to actively recruit myoblasts nearly as well as wild-type MOLs. However, many of the hydroxyurea-affected MOL fibers were incapable of the normal male-specific expression of a muscle-specific reporter gene. We suggest that early events in MOL development, such as finding the correct muscle attachment points, are relatively insensitive to the number of MOL nuclei compared with later events, such as the sex-specific expression of a reporter gene.
In fruitless mutant males, MOL-position fibers are smaller and had substantially fewer nuclei compared to wild-type MOLs. Since the number and distribution of muscle precursors was the same in fruitless mutant and wild-type animals, we propose that one fru+ function is to direct the male-specific recruitment of myoblasts into MOL-myotubes. However, fruitless+ must have more than one role in MOL fiber development, since simple reduction in the number of muscle nuclei, as demonstrated by the hydroxyurea ablations, is insufficient to account for all of the MOL muscle phenotypes in fruitless mutant males.
Genetic determinants of sense organ identity in Drosophila: regulatory interactions between cut and poxn
Authors: Vervoort Michel , Zink Daniele , Pujol Nathalie , Victoir Kathleen , Dumont Nathalie , Ghysen Alain , Dambly-Chaudière Christine 
Published: April 2021

ABSTRACT
Two genes involved in defining the type of sense organ have been identified in Drosophila. The gene cut differentiates the external sense organs (where it is expressed) from the chordotonal organs (where it is not); among the external sense organs poxn differentiates the poly-innervated organs (where it is expressed) from the mono-innervated organs (where it is not). Here we show that the expression of poxn in normal embryos does not depend on cut, and that poxn is capable of inducing the expression of cut. We have identified a small domain of the very large cut regulatory region as a likely target for activation by poxn.
Alterations in somite patterning of Myf-5-deficient mice: a possible role for FGF-4 and FGF-6
Authors: Grass Stefanie , Arnold Hans-Henning , Braun Thomas 
Published: April 2021

ABSTRACT
Mice carrying a targeted mutation in the gene for the myogenic factor Myf-5 fail to form major parts of the ribs, which leads to an unstable thorax and perinatal death. Here, we report that somites of Myf-5-deficient mice lack the expression of FGF-4 and FGF-6 while TGFβ-2 is expressed normally. Early sclerotomal markers, such as Pax-1 reveal no substantial reduction of sclerotome size. At E11.5 the condensing mesenchyme of the rib anlagen is considerably reduced in size in Myf-5 mutant mice. This may be caused by the lack of Myf-5-positive, FGF-expressing cells which normally are in close contact with the lateral sclerotome generating the rib progenitors. The potential role of FGFs and TGFβ on sclerotome formation is demonstrated in micromass cultures of early somites. Combinations of FGF-4 or FGF-6 with TGFβ-2 potentiate chondrogenesis suggesting that these growth factors emanating from early myotomal and dermomyotomal cells may have instructive or permissive effects on differentiation or outgrowth of sclerotomal cells.