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The influence of Hox genes and three intercellular signalling pathways on enteric neuromuscular development


Raj P. Kapur, MD, PhD, Department of Laboratories, 6P-1, Children's Hospital and Regional Medical Center, 4800 Sand Point Way NE, Seattle, Washington 98105, USA.
Tel.: (206) 987 2103; fax: (206) 987 3840;


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.