Lecoin L, Gabella G, Le Douarin N
Institut d'Embryologie Cellulaire et Moléculaire du CNRS et du collège de France, Nogent sur Marne.
Development. 1996 Mar;122(3):725-33. doi: 10.1242/dev.122.3.725.
Interstitial cells of Cajal (ICC) aroused much interest among neuroanatomists at the beginning of the century. These small cells, organized into networks, are intercalated between nerve fibers and muscle cells, and are now considered by many authors to be responsible for the pacemaker activity of the gut. Renewed interest in these cells arose recently when the receptor tyrosine kinase, c-kit, was shown to be associated with their functional activity. The embryonic origin of interstitial cells has remained a controversial issue ever since their discovery. Some authors consider them to be of neural or glial nature and thus of neural crest origin. Others consider them to be of fibroblastic or muscular nature. We have applied the quail-chick marker system to solve this problem. ICC were identified by means of a chicken-c-kit nucleic probe which cross-reacts with the quail c-kit gene product. We constructed chimeric bowels by grafting isotopically quail vagal neural crest into chick embryos at embryonic day 2 (E2). The enteric innervation of the chimeras was then of quail origin. In situ hybridization of the chimeric bowels showed that all the c-kit-positive cells were of the chick type, and therefore belonged to the gut mesenchyme and were not neural crest-derived cells. This observation was confirmed by culturing aneural chick guts on the chorio-allantoic membrane. Typical ICC, as defined at the EM level and by their expression of the c-kit receptor, developed in the gut wall in the complete absence of enteric innervation. One can conclude the ICC are of mesodermal origin and develop independently from enteric neurons with which they later establish anatomical and functional relations.
世纪初， Cajal间质细胞（ICC）就引起了神经解剖学家的浓厚兴趣。这些小细胞组成网络，插在神经纤维和肌肉细胞之间，现在许多作者认为它们负责肠道的起搏活动。最近，当受体酪氨酸激酶c-kit被证明与其功能活动相关时，人们对这些细胞重新产生了兴趣。自从间质细胞被发现以来，其胚胎起源一直是个有争议的问题。一些作者认为它们具有神经或神经胶质性质，因此起源于神经嵴。另一些人则认为它们具有成纤维细胞或肌肉性质。我们应用鹌鹑-鸡标记系统来解决这个问题。通过与鹌鹑c-kit基因产物发生交叉反应的鸡c-kit核酸探针来鉴定ICC。我们在胚胎第2天（E2）将同位素标记的鹌鹑迷走神经嵴移植到鸡胚中，构建嵌合体肠道。然后，嵌合体的肠神经支配来自鹌鹑。对嵌合体肠道进行原位杂交显示，所有c-kit阳性细胞都是鸡型的，因此属于肠间充质，而不是神经嵴衍生细胞。在绒毛尿囊膜上培养无神经的鸡肠道证实了这一观察结果。在完全没有肠神经支配的情况下，肠壁中发育出了在电子显微镜水平和通过其c-kit受体表达所定义的典型ICC。可以得出结论，ICC起源于中胚层，独立于肠神经元发育，随后与肠神经元建立解剖学和功能关系。
