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At least 145 records · Page 8Linked to original sources

PubMed1987

Hypothyroidism disrupts neural development in the olfactory epithelium of adult mice.

Adult mice made hypothyroid with propylthiouracil (PTU) lose their sense of smell. This is prevented by daily administration of thyroxine. As thyroxine is necessary for the correct development of the nervous system it may also be necessary for the genesis of new olfactory receptor neurones, a process that continues into adulthood. Adult mice were treated with PTU, injected with [3H]thymidine after 54 days and killed 5 or 15 days later. Microscopic analysis of the olfactory epithelium after autoradiography revealed similar numbers of labelled nuclei in the basal cell layer of the olfactory epithelia of Control and Hypothyroid mice 5 days after injection with [3H]thymidine. This indicated similar rates of basal cell division in the two groups. Fifteen days after [3H]thymidine injection, however, there were fewer labelled nuclei in the receptor cell layer of Hypothyroid mice and the olfactory epithelium was thinner than in Controls. Thyroxine therapy which reversed PTU-induced anosmia also reversed the epithelial effects of PTU treatment. Somewhat unexpectedly, there were no differences between the treatment groups in the average diameter of glomeruli in the olfactory bulb, and no differences in the expression of olfactory marker protein. The results indicate that although hypothyroidism disrupts neural development in the olfactory epithelium, it does not lead to a complete loss of mature receptor neurones.

Animals↗

PubMed2006

Smooth muscle cell apoptosis and defective neural development in congenital ureteropelvic junction obstruction.

PURPOSE: We assessed the smooth muscle cell apoptosis along with changes in cellular and extracellular components of the ureteropelvic junction in 23 patients with unilateral obstruction and compared them with 25 autopsies from ureteropelvic junction regions of age matched cadavers. MATERIALS AND METHODS: Tissue specimens obtained from pyeloplasty were divided into 3 sections-renal pelvis above the obstruction, obstructed ureteropelvic junction and ureter below the obstructed region. For the control group the normal ureteropelvic junctions of age matched infants were autopsied. In paraffin embedded sections we determined myocyte apoptosis index (using TUNEL assay), and the amount of muscular components and nerve terminals (using image analysis techniques after immunohistochemical staining). The collagen and elastin fibers were specifically stained for evaluation of changes in extracellular matrix. RESULTS: Smooth muscle cell apoptosis index was significantly increased at the site of ureteropelvic junction obstruction (5.68 +/- 0.18) compared to normal autopsied ureteropelvic junctions (3.60 +/- 0.11) and 2 other sections of obstructed ureteropelvic junction complex (renal pelvis 4.73 +/- 0.16, and ureter 3.97 +/- 0.16). The number of nerve terminals and the percentage of muscular component were significantly lower at the obstructed segments of affected patients compared to normal ureteropelvic junctions. Meanwhile, collagen fibers formed a significantly higher proportion of ureteral wall at the site of obstruction. Interestingly, there was negative correlation between myocyte apoptosis indices and number of nerve endings as well as amount of muscular components at the site of ureteropelvic junction obstruction. However, positive correlations were found between smooth muscle cell apoptosis and the percentage of collagen and elastin fibers. CONCLUSIONS: Our findings suggest an important role for myocyte apoptosis and defective neural development in the pathogenesis of congenital ureteropelvic junction obstruction that could pave the road for the emergence of new therapeutic modalities.

Abnormalities, Multiple↗

PubMed2006

Cholesterol homeostasis in development: the role of Xenopus 7-dehydrocholesterol reductase (Xdhcr7) in neural development.

7-dehydrocholesterol reductase (7-Dhcr) catalyses the final step in the pathway of cholesterol biosynthesis. Human patients with inborn errors of 7-Dhcr (Smith-Lemli-Opitz-Syndrome) have elevated serum levels of 7-dehydrocholesterol but low levels of cholesterol, which in phenotypical terms can result in growth retardation, craniofacial abnormalities including cleft palate, and reduced metal abilities. This study reports the isolation and molecular characterisation of 7-dehydrocholesterol reductase (Xdhcr7) from Xenopus laevis. During early embryonic development, the expression of Xdhcr7 is first of all spatially restricted to the Spemann's organizer and later to the notochord. In both tissues, Xdhcr7 is coexpressed with Sonic hedgehog (Shh), which itself is cholesterol-modified during autoproteolytic cleavage. Data from Xdhcr7 overexpression and knockdown experiments reveals that a tight control of cholesterol synthesis is particularly important for proper development of the central and peripheral nervous system.

Alternative Splicing↗

PubMed1989

The absence of a relation between the periconceptional use of vitamins and neural-tube defects. National Institute of Child Health and Human Development Neural Tube Defects Study Group.

Whether taking multivitamins or folate around the time of conception can reduce a woman's risk of having a child with a neural-tube defect is controversial. To investigate this question, we examined the periconceptional use of vitamin supplements by women who had a conceptus with a neural-tube defect (n = 571), women who had had a stillbirth or a conceptus with another malformation (n = 546), and women who had had a normal conceptus (n = 573). Women with conceptuses with neural-tube defects were identified either prenatally or postnatally and were matched to control mothers for gestational age. To minimize recall bias, we interviewed nearly all the women within five months of the diagnosis of a birth defect or the birth of the infant (mean, 84 days); information on vitamin use was obtained by an interviewer who was unaware of the outcome of pregnancy. The rate of periconceptional multivitamin use among the mothers of infants with neural-tube defects (15.8 percent) was not significantly different from the rate among mothers in either the abnormal or the normal control group (14.1 percent and 15.9 percent, respectively). After adjustment for potential confounding factors, the odds ratio for having an infant with a neural-tube defect among women classified as having had full supplementation with multivitamins was 0.95 as compared with the mothers of the abnormal infants (95 percent confidence interval, 0.78 to 1.14) and 1.00 as compared with the mothers of normal infants (95 percent confidence interval, 0.83 to 1.20). There were no differences among the groups in the use of folate supplements. The adjusted odds ratio for having an infant with a neural-tube defect among those receiving the recommended daily allowance of folate was 0.97 as compared with the mothers of abnormal infants (95 percent confidence interval, 0.79 to 1.18) and 0.98 as compared with the mothers of normal infants (95 percent confidence interval, 0.80 to 1.20). We conclude that the periconceptional use of multivitamins or folate-containing supplements by American women does not decrease the risk of having an infant with a neural-tube defect.

Adult↗

PubMed2001

Roles, regulation, and mechanism of polysialic acid function during neural development.

The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) appeared during the evolution of vertebrates as a new mechanism for regulation of cell interactions. This large and abundant glycoprotein can exert steric effects at the cell surface that lead to the attenuation of cell-cell bonds mediated not only by NCAM but also a variety of other adhesion receptors. PSA-NCAM expression changes both as a result of developmental programs and physiological inputs. This global modulation of cell-cell attachment has been shown to facilitate cell migration, axon pathfinding and targeting, and plastic changes in the embryonic and adult nervous system.

Animals↗

PubMed2006

Cellular and molecular analysis of neural development of glycosyltransferase gene knockout mice.

Recent studies demonstrate that carbohydrates synthesized by specific glycosyltransferases play important roles in the development of the central nervous system. Among these carbohydrates, polysialic acid is a unique glycan that modulates functions of the neural cell adhesion molecule (NCAM) by attenuating NCAM-mediated interaction between neural cells. During brain development, polysialic acid is synthesized in a specific spatiotemporal pattern by two polysialyltransferases, ST8SiaII and ST8SiaIV. To study in vivo the roles of polysialic acid synthesized by each respective enzyme, we generated ST8SiaII and ST8SiaIV knockout mice. Single knockout ST8SiaII or ST8SiaIV mice show polysialic acid expression patterns differing from wild type, and those patterns indicate different roles of each gene during neural development. In this chapter, we discuss methods used to analyze polysialyltransferase knockout mice using immunohistochemistry of brain and primary cultures of neurons.

Animals↗

PubMed1994

Localization of CRABP-I and CRABP-II mRNA in the early mouse embryo by whole-mount in situ hybridization: implications for teratogenesis and neural development.

Retinoic acid (RA) has been implicated in vertebrate neural pattern formation. In this paper we analysed the expression patterns of the cellular retinoic acid binding proteins (CRABP-I and II) during early morphogenesis in normal and RA-treated mouse embryos by whole-mount in situ hybridization. This technique allowed a detailed analysis of the spatial and temporal changes in mRNA expression pattern. Both CRABPs were expressed in a rhombomere specific pattern; putative neural crest cells in the branchial arches expressed the CRABPs at levels corresponding to the rhombomere from which they were derived. CRABP-II, but not CRABP-I, was expressed in the neural epithelium caudal to the hindbrain. CRABP-I is strongly expressed in a fine net-like pattern which extends from the caudal diencephalon to the rostral hindbrain and remains predominantly dorsal to the lateral midline of the neural tube. This network corresponds to the pattern formed by the putative first axons of the embryonic mouse brain which are produced by the developing neurons of the mesencephalic nucleus of the trigeminal nerve. Although the expression of CRABP-I was unaffected by a teratogenic dose of RA, CRABP-II expression was increased slightly with no alteration in the normal spatial or temporal boundaries. These results support the suggestion that the CRABPs may play an important role in modulating endogenous RA levels, particularly in the developing nervous system and its neural crest derivatives. Furthermore, the limited ability of CRABP mRNA levels to respond to exogenous retinoids may be a factor in retinoid teratogenicity.

Abnormalities, Drug-Induced↗

PubMed2000

Role of presenilin-1 in murine neural development.

Our previous studies showed that presenilin-1 (PS1) is required for murine neural and skeletal development. Here we report that the reduction in the neural progenitor cells observed in the PS1-/- mouse brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In the ventricular zone of PS1-/- mice, expression of the Notch1 downstream effector gene Hes5 is reduced, and expression of the Notch1 ligand Dll1 is elevated, indicating reduced Notch signaling. These results provide direct evidence that PS1 is involved in the regulation of neurogenesis and Notch signaling during development.

Animals↗

PubMed1997

Neuregulins and neuregulin receptors in neural development.

The neuregulins are a family of closely related proteins that play important roles in neural and cardiac development, as well as in mammary carcinogenesis. The pleiotropic activities of these molecules are transduced by a set of receptor protein tyrosine kinases that exhibit structural similarity to the receptor for epidermal growth factor. Recent results have demonstrated essential roles for the neuregulins and their receptors in regulating cell number, determining cell fate, and establishing pattern in the developing central and peripheral nervous systems.

Animals↗

PubMed1997

HNMP-1: a novel hematopoietic and neural membrane protein differentially regulated in neural development and injury.

The hnmp-1 (hematopoietic neural membrane protein) gene encodes a protein with striking similarity to the tetra-transmembrane-spanning protein encoded by pmp22. hnmp-1 was cloned from an elutriated human monocyte library and is expressed in various human hematopoietic and lymphoid lineages as well as adult mouse spleen and thymus. In the mouse nervous system, HNMP-1 mRNA is temporally expressed by Schwann cells during sciatic nerve myelination. Dorsal root ganglia sensory and spinal cord alpha-motoneurons acquire HNMP-1 protein selectively throughout development. In the fiber tracts of the spinal cord and in sciatic nerve, HNMP-1 protein is axon-associated. Additionally a rapid and sustained level of HNMP-1 expression is observed in response to acute PNS injury. HNMP-1 is constituitively induced in sciatic nerve of Trembler J mice, which are mutant for pmp22 and have a demyelinating/hypomyelinating phenotype. The expression pattern of HNMP-1 suggests a possible role for this molecule during active myelination.

Amino Acid Sequence↗

PubMed2006

The Xfeb gene is directly upregulated by Zic1 during early neural development.

The transcription factor Zic1 plays important roles in patterning the neural plate in early vertebrate development. However, few genes that are regulated by Zic1 are known. We have identified a new direct downstream target gene of Zic1 that we have named Xfeb. Xfeb is a member of the pathogenesis-related (PR) protein superfamily and contains five tandem SCP domains. The sequence of Xfeb suggests that it may possess serine protease activity. Xfeb is expressed in the presumptive hindbrain region during neurula stages and in somite tissues later in development. Xfeb represses the hindbrain gene hoxB1 and the anterior neural gene otx2, suggesting that Xfeb is involved in regionalizing the neural plate, possibly by ensuring a posterior expression limit for otx2.

Amino Acid Sequence↗

PubMed1991

Expression of two members of the Wnt family during mouse development--restricted temporal and spatial patterns in the developing neural tube.

The Wnt gene family encodes a group of cysteine-rich proteins implicated in intercellular signaling during several stages of vertebrate development. This family includes Wnt-1 and Wnt-3, both discovered as activated oncogenes in mouse mammary tumors. Here we describe the molecular cloning of an additional member of the Wnt family, called Wnt-3A, and the spatial and temporal expression pattern of this gene as well as that of its close relative Wnt-3. The putative amino acid sequences of both proteins are almost 90% identical, but in situ hybridization to mouse embryo sections showed highly restricted patterns of expression of Wnt-3 and Wnt-3A, largely in separate areas in the developing nervous system. In the spinal cord Wnt-3 was expressed at low levels in the alar laminae and in the ventral horns, whereas Wnt-3A expression was confined to the roof plate. In the developing brain Wnt-3 was expressed broadly across the dorsal portion of the neural tube with a rostral boundary of expression at the diencephalon. In contrast, Wnt-3A was expressed in a narrow region very close to the midline; expression extended into the bifurcating telencephalon, in a highly localized fashion. Both Wnt-3 and Wnt-3A were expressed in the ectoderm, and Wnt-3A was also expressed in the periumbilical mesenchyme. Characteristic expression patterns of these two closely related genes suggest that Wnt-3 and Wnt-3A play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube.

Amino Acid Sequence↗

PubMed1987

Neurochemical characterization of embryonic brain development in trisomy 19 (Ts19) mice: implications of selective deficits observed for abnormal neural development in aneuploidy.

In this study, we examined the neurochemical profiles of selected brain regions (cerebral hemispheres, diencephalon/brainstem) in fetal (day 14 to 18 gestation) trisomy 19 (Ts19) mice. The neurochemical characteristics we observed in Ts19 mice were quite different from those we observed previously in Ts16 mice. Choline acetyltransferase (ChAT) activity was reduced significantly in the cerebral hemispheres, but not in the brainstem/diencephalon, of the fetal Ts19 mouse brain, suggesting a selective vulnerability of telencephalic cholinergic neurons. Additionally, the activity of glutamic acid decarboxylase (GAD) was reduced significantly in both hemispheres and diencephalon/brainstem of late gestation Ts19 fetuses, suggesting a selective vulnerability of GABAergic neurons as well. While the levels of catecholaminergic and dopaminergic markers were reduced significantly at late gestational ages, the relative rate of turnover of dopamine (DA), measured by the ratio of DOPAC/DA, was elevated significantly in Ts19 mice. Neither reduction in the thickness of various cellular zones of the cerebral cortex nor reduced cell density of the cerebral cortex accounts for the alterations in neurochemical parameters observed in Ts19 mice. These results suggest that the effects of the triplication of specific genes on the respective chromosomes, rather than a generalized disruption of developmental homeostasis resulting from extra chromosomal material, may produce selective alterations in neurochemical and neuroanatomical markers observed in these two mouse trisomies.

Aneuploidy↗

PubMed2000

Mice deficient in the polysialyltransferase ST8SiaIV/PST-1 allow discrimination of the roles of neural cell adhesion molecule protein and polysialic acid in neural development and synaptic plasticity.

Functional properties of the neural cell adhesion molecule (NCAM) are strongly influenced by polysialylation. We used gene-targeting to generate mice lacking ST8SiaIV/PST-1, one of the polysialyltransferases responsible for addition of polysialic acid (PSA) to NCAM. Mice homozygous for the null mutation reveal normal development of gross anatomical features. In contrast to NCAM-deficient mice, olfactory precursor cells in the rostral migratory stream express PSA and follow their normal pathway. Furthermore, delamination of mossy fibers in the hippocampal CA3 region, as found in NCAM-deficient mice, does not occur in ST8SiaIV mutants. However, during postnatal development these animals show a decrease of PSA in most brain regions compared to wild-type animals. Loss of PSA in the presence of NCAM protein but in the absence of obvious histological changes allowed us to directly address the role of PSA in synaptic plasticity. Schaffer collateral-CA1 synapses, which express PSA in wild types, showed impaired long-term potentiation (LTP) and long-term depression (LTD) in adult mutants. This impairment was age-dependent, following the time course of developmental disappearance of PSA. Contrary to NCAM mutant mice, LTP in ST8SiaIV mutants was undisturbed at mossy fiber-CA3 synapses, which do not express PSA in wild-type mice. The results demonstrate an essential role for ST8SiaIV in synaptic plasticity in hippocampal CA1 synapses, whereas PSA produced by different polysialyltransferase or polysialyltransferases at early stages of differentiation regulates migration of neural precursor cells and correct lamination of mossy fibers. We suggest that NCAM but not PSA is likely to be important for LTP in the hippocampal CA3 region.

Aging↗

PubMed1998

Expression of protein kinase C gene family members is temporally and spatially regulated during neural development in vitro.

We used primary cultures of rat hippocampal neurons and PCC7-Mz1 cells to correlate the expression of the protein kinase C (PKC) gene family with specific events during neural differentiation. Multipotent PCC7-Mz1 embryonic carcinoma stem cells develop into a tissue-like pattern of neuronal, fibroblast-like and astroglial cells by all-trans retinoic acid (RA) treatment. Western blot analyses demonstrate that PKCalpha, betaI, gamma, theta, mu, lambda, and zeta were constitutively expressed but the expression of PKCbetaII, delta, epsilon, and eta was up-regulated three days after addition of RA when cells mature morphologically. While the protein levels of the PKC isoforms betaII, delta and eta decreased after d6, when the major phenotypical alterations of the developing neurons were completed, PKCepsilon expression remained at a high level. Immunofluorescence studies demonstrated that PKCalpha, lambda and zeta were constantly expressed in stem cells and the arising cell types. PKCdelta was detected in all differentiated cell types, whereby PKCbetaII, gamma, epsilon, and zeta were solely found in the neuronal derivatives with PKCgamma predominantly located in the nuclei. PKCeta was weakly expressed at the Golgi complex of stem cells but expanded throughout the entire somata of all developing neurons. In contrast, PKCbetaII was abundant only in the somata of a minor fraction of all neurons (approximately 2.5%). Also, PKCepsilon was exclusively synthesized by a subpopulation of neurons (40+/-5%), where it was localized in the somata and in the axons. PKCzeta was persistently expressed in two forms, the full-length PKCzeta and the constitutively active, proteolytic product PKMzeta, reasoning that permanent PKCzeta activity is important for PCC7-Mz1 physiology. Fractionation of extracts from undifferentiated and differentiating PCC7-Mz1 cells revealed that the conventional cPKCalpha was partly and the cPKCbetaI and the novel nPKCs delta and epsilon were mainly membrane bound, implying that they were also in an active state. However, when using the PKC substrate MARCKS (myristoylated alanine-rich C kinase substrate) to monitor cellular PKC activity, we observed that activation of PKC by phorbol ester was required for complete MARCKS phosphorylation and its translocation from the membrane to the cytoplasm. Our data show that the cell type-specific expression, subcellular localization and activation of PKCs are regulated in an isoform-specific manner during neurogenesis suggesting that they are involved in the control of neural development and in particular in neuronal differentiation.

Animals↗

PubMed1994

Sex hormone modulation of neural development in vitro.

The sex hormonal milieu during human and primate development is thought to influence adult cognition, perception, and behavior. Similarly in the rat, the neonatal sex hormonal milieu dictates adult behavior, as well as patterns of neural organization within the CNS. Specifically, estrogen and androgen alter neurite outgrowth, neuritic spine development, and synaptogenesis in the limbic system and spinal cord. To examine specific molecular/cellular effects of sex hormones on neurons, in vitro models were developed, using the PC12 cell line. Wild-type cells (PC12-WT) were stably transfected either with an expression vector coding for the human estrogen receptor (ER), androgen receptor (AR), or with a control vector. Resultant clones were isolated, screened for incorporation of vector and expression of ER or AR mRNA and protein, and analyzed for morphologic responses to estrogen and androgen, respectively. PC12-WT, NEO9 (ER-negative, AR-negative), SER8 (ER-positive, AR-negative), and AR8 (ER-negative, AR-positive) cells were exposed to nerve growth factor and graded doses of estradiol or dihydrotestosterone (DHT) for 2 days. In SER8 cells, estradiol led to dose-dependent increases in the frequency of neurite outgrowth, spine development, and interneuritic connectivity. Estradiol increased the frequency of gap junction frequency and length, and functional dye-coupling in SER8 cells. Conversely, in AR8 cells, DHT induced a dose-dependent increase in mean neurite length, branch order, and neuritic field area, while neurite branch segment length and soma area were unaffected. These results suggest that SER8 and AR8 cells in vitro recapitulate various sex hormonal effects on neurons in vivo. Estrogen and androgen appear to induce inherent neural morphologic programs in which androgen increases neurite arborization and the receptive field of individual cells, increasing the likelihood for intercellular communication, while estrogen actually induces this communication, in the form of spines, synapses, and gap junctions. Thus estrogen and androgen act in different but complementary ways to modulate neural development and organization.

Androgens↗

PubMed1990

Expression of adhesion molecules and the establishment of boundaries during embryonic and neural development.

Evidence is accumulating that molecules involved in cell-cell and cell-substratum interactions are important in the establishment and maintenance of borders between cell groups during development. In this report, we review evidence supporting this conclusion, particularly in regard to the role of adhesion molecules in the formation of cell collectives and in the modulation of cell and neurite movements.

Animals↗

PubMed2006

Expression of AmphiPOU-IV in the developing neural tube and epidermal sensory neural precursors in amphioxus supports a conserved role of class IV POU genes in the sensory cells development.

POU genes play a prominent role in the nervous system differentiation of several organism models, and in particular, they are involved in the differentiation of sensory neurons in numerous invertebrate and vertebrate species. In the present report, cloning and expression profile of a class IV POU gene in amphioxus was assessed for understanding its role in the sensory systems development. A single class IV gene, AmphiPOU-IV was isolated from the amphioxus Branchiostoma floridae. From a phylogenetic point of view, AmphiPOU-IV appears to be strictly related to the vertebrate one, sharing a high homology ratio especially with all vertebrate POU-IV proteins Brn-3a, Brn-3b, and Brn-3c. AmphiPOU-IV was found in the most anterior neural plate and in scattered ectodermic cells on the flanks of neurula, such ectodermic cells resemble the characteristic morphology and position of AmphiCoe and AmphiTrk developing sensory cells. Later on, the expression was confined in some motoneurons at level of the PMC and in some segmental arranged motoneurons in the hindbrain. Such expression is also maintained in larvae, and a new site of AmphiPOU-IV expression was also found in rostrum and mouth edge epidermal sensory cells of the larva. In conclusion, our data suggest an evolutionary conserved role of POU-IV transcription factors in the specification and differentiation of the sensory system in both vertebrates and invertebrates and underline the importance of amphioxus as linking step between them.

Amino Acid Sequence↗