Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system
Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system
复制标题
DOI：
10.1016/j.ydbio.2006.01.032
复制
发表时间：
2006-05-01
影响因子：
2.7
通讯作者：
Goldstein, AM
中科院分区：
文献类型：
--
作者：
Nagy, N;Goldstein, AM
神经嵴细胞（NCC）在胃肠道壁内迁移、增殖和分化，形成肠神经系统（ENS）的神经元和神经胶质细胞。肠道微环境在这一过程中至关重要，内皮素-3 （ET3）在其中起着重要作用。该基因突变导致啮齿动物远端肠神经节病，但其作用机制尚不清楚。我们发现，在培养的禽肠中，抑制ET3信号也会导致后肠神经节病。本研究的目的是确定ET3在禽后肠ens形成过程中的作用。为了回答这个问题，我们将节前鹌鹑后肠移植到鸡胚的体腔中，建立了鸡-鹌鹑肠道嵌合体。鹌鹑移植物发育两个神经节神经丛，由分化的神经元和完全来自宿主神经嵴的胶质细胞组成。移植物中过量ET3的存在导致神经节细胞数量显著增加，而内皮素受体b （EDNR-B）的抑制导致严重的神经节减少症。et3诱导的神经节过多症与肠嵴细胞增殖增加有关。利用胶原凝胶培养的后肠外植体，我们发现ET3还能抑制ens中的神经元分化。最后，在盲肠中强烈表达的ET3能抑制NCC对胶质源性神经营养因子（GDNF）的化学吸引。我们的研究结果表明，ET3信号在禽类后肠ENS发育过程中发挥了多种作用，影响了NCC的增殖、分化和迁移。(c) 2006爱思唯尔公司版权所有。
Neural crest cells (NCC) migrate, proliferate, and differentiate within the wall of the gastrointestinal tract to give rise to the neurons and glial cells of the enteric nervous system (ENS). The intestinal microenvironment is critical in this process and endothelin-3 (ET3) is known to have an essential role. Mutations of this gene cause distal intestinal aganglionosis in rodents, but its mechanism of action is poorly understood. We find that inhibition of ET3 signaling in cultured avian intestine also leads to hindgut aganglionosis. The aim of this study was to determine the role of ET3 during formation of the avian hindgut ENS. To answer this question, we created chick-quail intestinal chimeras by transplanting preganglionic quail hindguts into the coelomic cavity of chick embryos. The quail grafts develop two ganglionated plexuses of differentiated neurons and glial cells originating entirely from the host neural crest. The presence of excess ET3 in the grafts results in a significant increase in ganglion cell number, while inhibition of endothelin receptor-B (EDNR-B) leads to severe hypoganglionosis. The ET3-induced hyperganglionosis is associated with an increase in enteric crest cell proliferation. Using hindgut explants cultured in collagen gel, we find that ET3 also inhibits neuronal differentiation in the ENS. Finally, ET3, which is strongly expressed in the ceca, inhibits the chemoattraction of NCC to glial-derived neurotrophic factor (GDNF). Our results demonstrate multiple roles for ET3 signaling during ENS development in the avian hindgut, where it influences NCC proliferation, differentiation, and migration. (c) 2006 Elsevier Inc. All rights reserved.