Sculpting organ innervation

Hempstead, Barbara L.

doi:10.1172/jci21309

Cited by 9 publications

(7 citation statements)

References 23 publications

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“…However, this study raised the interesting possibility that Sprouty regulates GPCRligand mediated biological processes. It is notable that enteric nerve development is regulated by GDNF and endothelin-3 (Angrist et al, 1996;Hempstead, 2004). Therefore, the enteric nerve dysplasia phenotype of Sprouty2 KO mice may be partly explained by hypersignaling of ET-3 (Taketomi et al, 2005).…”

Section: Sprouty4 Inhibits Pip 2 Hydrolysis T Ayada Et Almentioning

confidence: 99%

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

et al. 2009

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Section: Sprouty4 Inhibits Pip 2 Hydrolysis T Ayada Et Almentioning

confidence: 99%

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

et al. 2009

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“…More recently, BDNF has been shown to act as a neuromodulator of the central rhythmogenic respiratory circuits (68,69).…”

Section: Expression Of Polycomb Group Genes In the Emc-eshoxa1-15mentioning

confidence: 99%

“…Although it has been reported that the physiological origin of this defect is the presence of an ectopic neuronal circuit affecting the respiration-controlling region in the brain of the mutant embryos (114), little is known about the molecular causes that lead to the alteration of normal neurogenesis in this region. The identification by microarray analyses of the putative Hoxa1 target gene, BDNF, whose gene product acts as a neuromodulator of the central rhythmogenic respiratory circuits (69), may provide an additional clue about the molecular events involved in the perinatal lethality of the Hoxa1 homozygous mice. Analysis of the expression of the additional brain-related Hoxa1 putative targets in this region of the brain in mutant embryos may help to elucidate the cascade of genetic events that induces the formation of novel neuronal circuits.…”

Section: Hoxa1 ϫ/ϫ Es Cells Express Lower Levels Of Genes Involved Inmentioning

confidence: 99%

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

Martinez‐Ceballos

Chambon

Gudas

2005

Journal of Biological Chemistry

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Homeobox (Hox) genes encode a family of transcription factors that regulate embryonic patterning and organogenesis. In embryos, alterations of the normal pattern of Hox gene expression result in homeotic transformations and malformations. Disruption of the Hoxa1 gene, the most 3 member of the Hoxa cluster and a retinoic acid (RA) direct target gene, results in abnormal ossification of the skull, hindbrain, and inner ear deficiencies, and neonatal death. We have generated Hoxa1 genes positioned at the 3Ј-end are expressed earlier and more anterior, whereas 5Ј-end genes are expressed at later times and more posterior (reviewed in Refs. 1 and 5). Colinear gene expression from these Hox gene clusters may involve an initial change in chromatin structure (histone modification and chromatin decondensation) of the entire loci, which would then facilitate the programmed expression of genes along the clusters by a progressive 3Ј to 5Ј change in higher order chromatin structure (6). Treatment of teratocarcinoma cells or embryonic stem cells with retinoic acid (RA), which acts via the retinoic acid receptors (RAR␣, -␤, and -␥ and their isoforms (reviewed in Refs. 7 and 8), results in the sequential activation of several Hox genes in a manner that resembles their positions in the clusters, e.g. 3Ј genes are activated before 5Ј genes (7-9). Moreover, our laboratory discovered the presence of a retinoic acid response element (RARE) in the 3Ј enhancer of the Hoxa1 gene (10 -13). This RARE is also functional in transgenic mice (14 -16). We also demonstrated that unlike F9 Wt cells, F9 RAR␥ Ϫ/Ϫ cells fail to express the Hoxa1 gene in response to RA (17). Alterations in the normal pattern of Hox gene expression in embryos result in homeotic transformations and malformations, and frequently, in perinatal lethality (3,18). For instance, the targeted inactivation in mice of both alleles of the most 3Ј member of the Hoxa cluster, the Hoxa1 gene, leads to numerous developmental defects, including hindbrain deficiencies and abnormal skull ossification, and ultimately, to neonatal death (19 -22). Numerous studies have demonstrated that the hindbrain defects in Hoxa1 Ϫ/Ϫ mice result in part from the failure of Hoxb1 to reach its anterior limit of expression at the presumptive rhombomere 3/rhombomere 4 (r3/4) boundary, which initiates a cascade of gene misexpression that results in the misspecification of the hindbrain compartments from r2 to r5 (23-26). Furthermore, the ectopic expression of Hoxa1 in transgenic mice leads to the ectopic activation of Hoxb1 in r2, produces anterior abnormalities, including the reorganization of the developing hindbrain, and ultimately results in embryonic death (27). These observations highlight the importance of the Hoxa1 gene and suggest that the regulatory effects of retinoids on cell growth and on embryonic patterning may be * This work was supported by National Institutes of Health Grants R01CA43796 (to L. J. G.) and UR 2U19HDO35466. The costs of publication of this article were defrayed in part by th...

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“…In the central nervous system (CNS), EDNs are expressed by endothelial cells (Yoshimoto et al 1990), neurones (Lee et al 1990), astrocytes (MacCumber et al 1990) and microglial cells (Wu et al 2006). EDNs regulate neuronal activity (Inoue et al 1989;Hempstead 2004), development (Yanagisawa et al 1998) and injury (Hama et al 1997;Siren et al 2000).…”

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confidence: 99%

Deficiency in Endothelin Receptor B Reduces Proliferation of Neuronal Progenitors and Increases Apoptosis in Postnatal Rat Cerebellum

et al. 2008

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Endothelins regulate cellular functions in the mammalian brain through the endothelin receptors A and B (EDNRA and EDNRB). In this study, we investigated the role of EDNRB on cell proliferation in the cerebellum by using the spotting lethal (sl) rat, which carries a naturally occurring deletion in the EDNRB gene. Proliferating cells in the three genotypes, wild-type (+/+), heterozygous (+/sl) and homozygous mutant (sl/sl) rats were labelled by intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) at postnatal day 2. The density of BrdU-positive cells (per mm(2)) in the external germinal layer of sl/sl rats (Mean +/- SEM, 977 +/- 388) was significantly reduced compared to +/+ (4915 +/- 631) and +/sl (2304 +/- 557) rats. Subsequently, we examined the effects of EDNRB mutation on neural apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labelling assay. This showed that the density of apoptotic cells in the cerebella of sl/sl rats (9.3 +/- 0.5/mm(2)) was significantly more increased than +/+ rats (4 +/- 0.7). The expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured with standard ELISA, but were unchanged in all genotypes. These results suggest that ENDRB mediates neural proliferation and have anti-apoptotic effects in the cerebellum of the postnatal rat, and that these effects are independent of changes in the expression of BDNF and GDNF. Our findings will lead to better understanding of the morphological changes in the cerebellum of Hirschsprung's disease patients with congenital EDNRB mutation.

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Sculpting organ innervation

Cited by 9 publications

References 23 publications

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

Sprouty4 negatively regulates protein kinase C activation by inhibiting phosphatidylinositol 4,5-biphosphate hydrolysis

Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

Deficiency in Endothelin Receptor B Reduces Proliferation of Neuronal Progenitors and Increases Apoptosis in Postnatal Rat Cerebellum

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