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骨形态发生蛋白受体在神经系统中的发育及其在调节trkC表达中的可能作用。

Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression.

作者信息

Zhang D, Mehler M F, Song Q, Kessler J A

机构信息

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

出版信息

J Neurosci. 1998 May 1;18(9):3314-26. doi: 10.1523/JNEUROSCI.18-09-03314.1998.

Abstract

Characterization of bone morphogenetic protein receptor (BMPR) expression during development is necessary for understanding the role of these factors during neural maturation. In this study, in situ hybridization analyses demonstrate that BMP-specific type I (BMPR-IA and BMPR-IB) and type II (BMPR-II) receptor mRNAs are expressed at significant levels in multiple regions of the CNS, cranial ganglia, and peripheral sensory and autonomic ganglia during the embryonic and neonatal periods. All three BMP receptor subunits are expressed within periventricular generative zones. BMPR-IA is more abundant than the other receptor subtypes, with widespread expression in the brain, cranial ganglia, and peripheral ganglia. By contrast, BMPR-IB mRNA displays significant expression within more restricted regions, including the anterior olfactory nuclei. BMPR-II mRNA exhibits peak expression within the cerebellar Purkinje cell layer and the hippocampus, as well as within cranial ganglia. The distribution of BMP receptors within large neurons in adult dorsal root ganglia suggested a possible role in regulating expression of the neurotrophin receptor trkC. This hypothesis was tested in explant cultures of embryonic day 15 (E15) and postnatal day 1 (P1) sympathetic superior cervical ganglia (SCG). Treatment of the E15 or the P1 SCG with BMP-2 induced expression of trkC mRNA and responsiveness of sympathetic neurons to NT3 as measured by neurite outgrowth. The pattern of expression of BMP receptors in embryonic brain suggests several potentially novel areas for further developmental analysis and supports numerous recent studies that indicate that BMPs have a broad range of cellular functions during neural development and in adult life.

摘要

了解骨形态发生蛋白受体(BMPR)在发育过程中的表达特征,对于理解这些因子在神经成熟过程中的作用至关重要。在本研究中,原位杂交分析表明,BMP特异性I型(BMPR-IA和BMPR-IB)和II型(BMPR-II)受体mRNA在胚胎期和新生期的中枢神经系统、颅神经节以及外周感觉和自主神经节的多个区域中均有显著表达。所有三种BMP受体亚基均在脑室周围生成区表达。BMPR-IA比其他受体亚型更为丰富,在脑、颅神经节和外周神经节中广泛表达。相比之下,BMPR-IB mRNA在包括前嗅核在内的更局限区域有显著表达。BMPR-II mRNA在小脑浦肯野细胞层和海马以及颅神经节中表达达到峰值。BMP受体在成年背根神经节大神经元中的分布表明其可能在调节神经营养因子受体trkC的表达中发挥作用。这一假设在胚胎第15天(E15)和出生后第1天(P1)的交感神经颈上神经节(SCG)外植体培养中得到了验证。用BMP-2处理E15或P1的SCG可诱导trkC mRNA的表达以及交感神经元对NT3的反应,反应通过神经突生长来衡量。BMP受体在胚胎脑中的表达模式提示了几个有待进一步发育分析的潜在新领域,并支持了众多近期研究,这些研究表明BMP在神经发育和成年期具有广泛的细胞功能。

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