ORIGIN OF THE C-KIT-POSITIVE INTERSTITIAL-CELLS IN THE AVIAN BOWEL

Interstitial cells of Cajal (ICC) aroused much interest among neuroana tomists 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 pace maker activity of the gut. Renewed interest in these cells arose recen tly when the receptor tyrosine kinase, c-kit, was shown to be associat ed with their functional activity, The embryonic origin of interstitia l cells has remained a controversial issue ever since their discovery. Some authors consider them to be of neural or glial nature and thus o f neural crest origin, Others consider them to be of fibroblastic or m uscular 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 constr ucted chimeric bowels by grafting isotopically quail vagal neural cres t into chick embryos at embryonic day 2 (E2). The enteric innervation of the chimeras was then of quail origin. In situ hybridization on 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 culturin g aneural chick guts on the chorioallantoic 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 innervat ion, One can conclude that ICC are of mesodermal origin and develop in dependently from enteric neurons with which they later establish anato mical and functional relations.