ORIGIN AND DIFFERENTIATION OF GUT ENDOCRINE-CELLS

The epithelium of the digestive tract contains endocrine cells which p roduce serotonin and an array of regulatory peptides. It is now irrefu tably established that gut endocrine cells are not of neural crest nor even of neurectodermal origin. Furthermore, the proposal that they mi ght originate from neuroendocrine-programmed epiblast has been refused by recent evidence that they share the endodermal stem cell pool with the other epithelial cells of the gut. Based on the available evidenc e, a working hypothesis for the differentiation of gut endocrine cells has been developed. It is proposed that initially the developing gut acquires an underlying tendency to differentiate into intestine: the e ndoderm has the potential to form a wide range of endocrine cell types . A little later, some influence operative over the length of the pres umptive gut imposes a regionally specific pattern on the tract. This p rocess concerns morphogenesis and pre-selection of the range and propo rtions of the endocrine cell types. Thereafter, the mesenchyme feeds t o the endoderm confirmatory signals reinforcing this pre-selected regi onal pattern of endocrine cells. Once the different endocrine cell typ es have started to differentiate, their maturation is effected by circ ulating factors which include glucocorticoid hormone: this process is mediated by the mesenchyme. Other factors concerned at various stages of gut endocrine cell differentiation could be other hormones, growth factors and or components of extracellular matrix: such factors are st ill untested in this context.