Roles of extracellular matrix in neural development.
Explore the source record for details and available documents.
Animals↗
SEARCH · PubMed Health
Results for “neural development”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Regulation of the inducible heat shock 71 genes in early neural development of cultured rat embryos.
Activation of the inducible heat shock 71 genes and their role in the heat shock response was studied in vitro in 9.5 day-old rat embryos at neural tube closure. The transcriptional response of a 71 kilodalton (kD) heat shock gene induced after various regimes of heat shock and acquired thermotolerance was investigated. Expression and accumulation of the heat shock (hs) 71 mRNA in the neuroectoderm was studied by Northern and dot blot analysis. Specific expression in various cell types and regions of the neuroectoderm were examined by in situ hybridization. Exposure of embryos to a heat shock at 43 degrees C for 7.5 min caused high levels of hs mRNA 71 accumulation in the neuroectoderm, pronounced protein synthesis inhibition, and regulated recovery. Specific neuroectoderm cell death followed, resulting in major developmental defects of the eye and forebrain region. A mild heat shock of 42 degrees C for 10 min induced the heat shock response, hsp synthesis, and cell recovery, but produced no cell death or deformities. Preheating the embryo at 42 degrees C resulted in acquired thermotolerance to an otherwise teratogenic 43 degrees C heat shock. Thermotolerance was associated with a rapid recovery of protein synthesis associated with hs 71 mRNA expression. Dot blot analysis showed that after a 42 degrees C heat shock, 71 mRNA was rapidly transcribed and transported into the cytoplasm where it was degraded within 2 hr of the initial response. The results suggest that the heat shock protein (hsp) 71 gene may have a protective rather than a rescuing function.
Animals↗
The RNA-binding protein Vg1 RBP is required for cell migration during early neural development.
After mid-blastula transition, populations of cells within the Xenopus embryo become motile. Using antisense morpholino oligonucleotides, we find that Vg1 RBP, an RNA-binding protein implicated in RNA localization in oocytes, is required for the migration of cells forming the roof plate of the neural tube and, subsequently, for neural crest migration. These cells are properly determined but remain at their site of origin. Consistent with a possible role in cell movement, Vg1 RBP asymmetrically localizes to extended processes in migrating neural crest cells. Given that Vg1 RBP is a member of the conserved VICKZ family of proteins, expressed in embryonic and neoplastic cells, these data shed light on the likely role of these RNA-binding proteins in regulating cell movements during both development and metastasis.
Animals↗
Cell adhesion molecules in the neural development and plasticity.
Cell adhesion molecules (CAMs) are cell surface glycoproteins mediating cell-cell and cell-matrix interactions which play a vital role in the embryonic development of the nervous system as well as in the maintenance and nerve regeneration in adults. In the central nervous system (CNS) three main CAMs, such as neural cell adhesion molecule (NCAM), L1 and N-cadherin have been characterized. In addition to their adhesive properties, CAMs are involved in cell migration, growth of axons, nerve pathways formation and synaptogenesis. The binding of CAMs can activate transmembrane-signalling reactions and thereby contribute to the initiation of cellular response in regulation of synaptic plasticity. CAMs play an important role in learning and memory. The role of CAMs in abnormal development and malignancies provide a wide field of research for diagnostic and therapeutic applications. (Ref. 36.)
Aging↗
BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time.
The formation of Alzheimer's Abeta peptide is initiated when the amyloid precursor protein (APP) is cleaved by the enzyme beta-secretase (BACE1); inhibition of this cleavage has been proposed as a means of treating Alzheimer's disease. (AD) We have previously shown that young BACE1 knockout mice (BACE1 KO) do not generate Abeta but in other respects appear normal. Here we have extended this analysis to include both gene expression profiling and phenotypic assessment of older BACE1 KO animals to evaluate the impact of chronic Abeta deficiency. We did not detect global compensatory changes in neural gene expression in young BACE1 KO mice. In particular, expression of the beta-secretase homolog BACE2 was not upregulated. Furthermore, we found no structural alterations in any organ, including all central and peripheral neural tissues, of BACE1 KO mice up to 14 months of age. Aged BACE1 KO mice engineered to overexpress human APP (BACE1 KO/APPtg) did not develop amyloid plaques. These data provide evidence that neither beta-secretase nor Abeta plays a vital role in mouse physiology and that chronic beta-secretase inhibition could be a useful approach in treating AD.
Amyloid Precursor Protein Secretases↗
Movements of mouse fetuses in early stages of neural development studied in vitro.
The transplacental perfusion method enables the in vitro maintenance and close observation of live mouse fetuses under conditions free of maternal influences. In the present study, this method was used to detect spontaneous movements of mouse fetuses in early developmental stages. When mouse fetuses at embryonic day (E) 12.5 were isolated together with the uterus and were maintained in vitro, they displayed periodic body movements that occurred every few minutes. Fetal movements were abolished after the application of drugs that depress neural activities. The present results obtained in in vitro mouse fetuses suggest that fetal movements and neural activities may be present during the early stages of motor system development and may play a role in the normal maturation of the motor systems.
Animals↗
[Effects of neural cell adhesion molecule and sulfated polysaccharides on the processes of neural development, neurite outgrowth, synaptic plasticity, learning and memory].
Explore the source record for details and available documents.
Animals↗
Ectopic neurons and aberrant connections during neural development.
During the normal development of the nucleus of origin of centrifugal fibers to the chick retina (the so-called isthmo-optic nucleus) a significant number of neurons are misrouted during their migration from the neural epithelium in which they are generated. Like the cells in the isthmo-optic nucleus, these ectopic neurons can be identified by the retrograde transport of horseradish peroxidase (donor: hydrogen peroxide oxidoreductase, EC 1.11.1.7) injected into the eye. Between 500 and 600 such cells have been identified on one side of the brain of 12 to 15-day-old embryos, but only about 10% of this number is seen beyond hatching. In addition, during development some of the cells in the nucleus send their axons to the ipsilateral retina, whereas in post-hatched animals they all project to the contralateral retina. The number of such neurons with aberrant axons is greatly increased (in some cases by as much as two orders of magnitude) in chicks from which one eye was removed early in development. Although normally about 60% of the neurons in the isthmo-optic nucleus degenerate between the 13th and 17th days of incubation, they can almost all be labeled by intraocular injections of horseradish peroxidase on the 12th day, indicating that the axons of virtually all the cells, including those neurone that subsequently die, reach the retina.
Age Factors↗
Strain differences in expression of the murine heat shock response: implications for abnormal neural development.
Explore the source record for details and available documents.
Animals↗
Can we develop neurally acting drugs for the treatment of migraine?
Serotonin (5-HT)(1B/1D) receptor agonists, which are also known as triptans, represent the most important advance in migraine therapeutics in the four millennia that the condition has been recognized. The vasoconstrictive activity of triptans produced a small clinical penalty in terms of coronary vasoconstriction but also raised an enormous intellectual question: to what extent is migraine a vascular problem? Functional neuroimaging and neurophysiological studies have consistently developed the theme of migraine as a brain disorder and, therefore, demanded that the search for neurally acting antimigraine drugs should be undertaken. The prospect of non-vasoconstrictor acute migraine therapies, potential targets for which are discussed here, offers a real opportunity to patients and provides a therapeutic rationale that places migraine firmly in the brain as a neurological problem, where it undoubtedly belongs.
Cardiovascular Physiological Phenomena↗
Hairless, a Drosophila gene involved in neural development, encodes a novel, serine rich protein.
Hairless is a dominant loss of function mutation in Drosophila affecting the formation of adult sensory organs. In the mutants, neuronal precursor cells do not differentiate, suggesting that Hairless might be involved in specifying or realizing neuronal fate in the fly, similar to the 'pro-neural' genes of the achaete-scute complex. As highlighted by the manifold phenotypic interactions of Hairless with most of the neurogenic loci, the gene might play an important role in nervous system development. Therefore, we initiated a molecular analysis of the Hairless locus in order to elucidate the function of its gene product and gain insight into the biochemical nature of the observed genetic interactions in which it participates. Here, we report the molecular cloning of the Hairless locus, confirmed by breakpoint and transformation analysis. Unexpectedly, Hairless activity peaks during embryogenesis, where transcripts accumulate primarily in endo- and mesodermal cell layers, and is lowest during larval stages, the lethal phase of Hairless mutants. The putative Hairless protein deduced from DNA sequencing is extremely basic and highly enriched in serine residues. Hairless appears to encode a novel protein without compelling homology to other known proteins which function in specifying peripheral nervous system development in Drosophila.
Amino Acid Sequence↗
The molecular genetics of Enhancer of split, a gene required for embryonic neural development in Drosophila.
In Drosophila, the very first steps in neurogenesis appear to be controlled by a small group of zygotically acting genes termed the neurogenic loci. Mutations in any of these genes result in a misrouting of epidermal lineages into the neural pathway. Morphological and molecular studies suggest that the correct ectodermal differentiation is mediated by a cell-cell interaction mechanism and that at least some of the neurogenic loci are involved in this mechanism. The molecular analyses of the neurogenic loci Notch and Delta revealed that the putative gene products are large transmembrane proteins with homology to mammalian epidermal growth factor. We describe here a molecular analysis of Enhancer of split [E(spl)], a third neurogenic locus, which displays striking genetic interactions with both Notch and Delta, suggesting a close functional relationship of the respective gene products. We provide evidence for a single genetic complementation group corresponding to a single transcription unit which is necessary for wild-type E(spl) function. P-element-mediated transformation indicates that this transcription unit includes functions associated with both the dominant E(spl)D mutation and the recessive visible allele groucho, and is necessary for the correct differentiation of the embryonic nervous system.
Animals↗
Active learning of enhancers and silencers in the developing neural retina.
Deep learning is a promising strategy for modeling cis-regulatory elements. However, models trained on genomic sequences often fail to explain why the same transcription factor can activate or repress transcription in different contexts. To address this limitation, we developed an active learning approach to train models that distinguish between enhancers and silencers composed of binding sites for the photoreceptor transcription factor cone-rod homeobox (CRX). After training the model on nearly all bound CRX sites from the genome, we coupled synthetic biology with uncertainty sampling to generate additional rounds of informative training data. This allowed us to iteratively train models on data from multiple rounds of massively parallel reporter assays. The ability of the resulting models to discriminate between CRX sites with identical sequence but opposite functions establishes active learning as an effective strategy to train models of regulatory DNA. A record of this paper's transparent peer review process is included in the supplemental information.
Retina↗
Crucial role of ecto-5'-nucleotidase in differentiation and survival of developing neural cells.
ATP, an important signalling substance in the central nervous system, is hydrolysed to adenosine via a surface-located enzyme cascade. The final hydrolysis step from AMP to adenosine is catalysed by 5'-nucleotidase, a GPI-anchored surface protein. 5'-Nucleotidase is transiently expressed on developing neurones. An antisense oligonucleotide that suppresses the synthesis of 5'-nucleotidase inhibits NGF-induced neurite formation and survival in PC12 cells and cultures of cerebellar granule cells. The inhibitory effect of the antisense oligonucleotide can be completely or partially relieved by addition of soluble 5'-nucleotidase or of nucleosides to the medium. Our results suggest that 5'-nucleotidase is essential for the differentiation and survival of neural cells and represents an important and critical step in the hydrolysis cascade of extracellular nucleotides.
5'-Nucleotidase↗
Ectopic expression of the bHLH gene Math1 disturbs neural development.
The basic helix-loop-helix gene Math1, a positive regulator of neuronal differentiation, is specifically expressed in the dorsal part of the developing nervous system. To determine the effects of ectopic expression of Math1, we generated two transgenic mouse lines; One carried the Cre recombinase gene under the control of the nestin promoter and enhancer, which direct expression in neural precursor cells, and the other carried the Math1 gene, the expression of which was regulated by the cytomegalovirus (CMV) promoter but interrupted by the stop cassette flanked by loxP sites. In F1 embryos that carried the two transgenes, the stop cassette was removed by Cre recombinase in the developing nervous system, and Math1 expression was ectopically directed from the CMV promoter. We found that these embryos exhibited abnormal morphology of the brain and extensive cell death in the nervous system. These results suggest that ectopic expression of Math1 is toxic to neurons and leads to apoptosis.
Animals↗
Reciprocity of structure-function relations in developing neural networks: the Odyssey of a self-organizing brain through research fads, fallacies and prospects.
Explore the source record for details and available documents.
Animals↗
Visualization of spatiotemporal activation of Notch signaling: live monitoring and significance in neural development.
Notch signaling plays various key roles in cell fate determination during CNS development in a context-dependent fashion. However, its precise physiological role and the localization of its target cells remain unclear. To address this issue, we developed a new reporter system for assessing the RBP-J-mediated activation of Notch signaling target genes in living cells and tissues using a fluorescent protein Venus. Our reporter system revealed that Notch signaling is selectively activated in neurosphere-initiating multipotent neural stem cells in vitro and in radial glia in the embryonic forebrain in vivo. Furthermore, the activation of Notch signaling occurs during gliogenesis and is required in the early stage of astroglial development. Consistent with these findings, the persistent activation of Notch signaling inhibits the differentiation of GFAP-positive astrocytes. Thus, the development of our RBP-J-dependent live reporter system, which is activated upon Notch activation, together with a stage-dependent gain-of-function analysis allowed us to gain further insight into the complexity of Notch signaling in mammalian CNS development.
Animals↗
dissatisfaction, a gene involved in sex-specific behavior and neural development of Drosophila melanogaster.
Few mutations link well defined behaviors with individual neurons and the activity of specific genes. In Drosophila, recent evidence indicates the presence of a doublesex-independent pathway controlling sexual behavior and neuronal differentiation. We have identified a gene, dissatisfaction (dsf), that affects sex-specific courtship behaviors and neural differentiation in both sexes without an associated general behavioral debilitation. Male and female mutant animals exhibit abnormalities in courtship behaviors, suggesting a requirement for dsf in the brain. Virgin dsf females resist males during courtship and copulation and fail to lay mature eggs. dsf males actively court and attempt copulation with both mature males and females but are slow to copulate because of maladroit abdominal curling. Structural abnormalities in specific neurons indicate a role for dsf in the differentiation of sex-specific abdominal neurons. The egg-laying defect in females correlates with the absence of motor neuronal innervation on uterine muscles, and the reduced abdominal curling in males correlates with alteration in motor neuronal innervation of male ventral abdominal muscles. Epistasis experiments show that dsf acts in a tra-dependent and dsx-independent manner, placing dsf in the dsx-independent portion of the sex determination cascade.
Abdomen↗