Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury
Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury
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DOI：
10.1172/jci58200
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发表时间：
2011-09-01
影响因子：
15.9
通讯作者：
Pachnis, Vassilis
中科院分区：
文献类型：
--
作者：
Laranjeira, Catia;Sandgren, Katarina;Pachnis, Vassilis
哺乳动物的肠神经系统（ENS）在胚胎发育和出生后早期由神经嵴细胞形成。然而，ENS的多能祖细胞可以在成人肠中使用克隆培养和体内移植测定来鉴定。这些神经源性前体在成人肠道的身份和它们的关系，胚胎祖细胞的ENS目前是未知的。使用遗传命运映射，我们在这里证明，小鼠神经嵴细胞标记SRY盒含基因10（Sox10）产生肠神经节的神经元和神经胶质细胞系。大多数神经元起源于妊娠中期肠道中的祖细胞。之后，肠神经发生减少，并在出生后1至3个月停止。Sox10表达细胞存在于成年小鼠的肌间神经丛表达胶质细胞标记物，我们没有发现证据表明，这些细胞在稳态条件下参与神经发生。然而，它们保留了神经原性潜力，因为它们能够在培养中产生具有肠神经元特征的神经元。此外，肠神经节的化学损伤后，肠神经胶质细胞在体内产生神经元。我们的研究结果表明，尽管在成人肠道组成性神经发生的情况下，肠神经胶质细胞保持有限的神经原性潜力，这可以被激活的组织解离或损伤。
The enteric nervous system (ENS) in mammals forms from neural crest cells during embryogenesis and early postnatal life. Nevertheless, multipotent progenitors of the ENS can be identified in the adult intestine using clonal cultures and in vivo transplantation assays. The identity of these neurogenic precursors in the adult gut and their relationship to the embryonic progenitors of the ENS are currently unknown. Using genetic fate mapping, we here demonstrate that mouse neural crest cells marked by SRY box-containing gene 10 (Sox10) generate the neuronal and glial lineages of enteric ganglia. Most neurons originated from progenitors residing in the gut during mid-gestation. Afterward, enteric neurogenesis was reduced, and it ceased between 1 and 3 months of postnatal life. Sox10-expressing cells present in the myenteric plexus of adult mice expressed glial markers, and we found no evidence that these cells participated in neurogenesis under steady-state conditions. However, they retained neurogenic potential, as they were capable of generating neurons with characteristics of enteric neurons in culture. Furthermore, enteric glia gave rise to neurons in vivo in response to chemical injury to the enteric ganglia. Our results indicate that despite the absence of constitutive neurogenesis in the adult gut, enteric glia maintain limited neurogenic potential, which can be activated by tissue dissociation or injury.