Kapur R P, Gershon M D, Milla P J, Pachnis V
Department of Pathology, Children's Hospital and Regional Medical Center, Seattle, USA.
Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:8-13. doi: 10.1111/j.1743-3150.2004.00467.x.
Normal intestinal motility requires orderly development of the complex nerve plexuses and smooth muscular layers in the gut wall. Organization of these structures results, in part, from cell autonomous programmes directed by transcription factors, which orchestrate appropriate temporal and spatial expression of specific target genes. Hox proteins appear to function in combination to dictate regional codes that establish major structural landmarks in the gut such as sphincters and muscle layers. These codes are translated in part by intercellular signals, which allow populations of cells in the embryonic gut wall to alter the developmental fate of their neighbours. Some of the best characterized intercellular signalling pathways involved in enteric neurodevelopment are mediated by GDNF/GFRa1/RET, EDN3/ENDRB, and NETRINS/DCC. These signals affect enteric neural precursors as they colonize the gut, and perturbations of these molecules are associated with various types of intestinal neuropathology.
正常的肠道蠕动需要肠壁中复杂神经丛和平滑肌层的有序发育。这些结构的组织部分源于由转录因子指导的细胞自主程序，转录因子协调特定靶基因在适当的时间和空间表达。Hox蛋白似乎共同发挥作用，决定区域编码，这些编码建立了肠道中的主要结构地标，如括约肌和肌肉层。这些编码部分通过细胞间信号进行转化，细胞间信号使胚胎肠壁中的细胞群体能够改变其邻居的发育命运。参与肠道神经发育的一些特征最明确的细胞间信号通路由GDNF/GFRa1/RET、EDN3/ENDRB和NETRINS/DCC介导。这些信号在肠道神经前体细胞定植肠道时影响它们，这些分子的扰动与各种类型的肠道神经病理学有关。
