Embryonic gut anomalies in a mouse model of retinoic acid-induced caudal regression syndrome - Delayed gut looping, rudimentary cecum, and anorectal anomalies

Vitamin A and its derivatives such as retinoic acid (RA) are important sign aling molecules for morphogenesis of vertebrate embryos. Little is known, h owever, about morphogenetic factors controlling the development of the gast rointestinal tract and RA is likely to be involved. In the mouse, teratogen ic doses of RA cause truncation of the embryonic caudal body axis that para llel the caudal regression syndrome as described in humans. These changes a re often associated with anomalies of the lower digestive tract. Overlappin g spatiotemporal expression of retinoic acid receptor-beta (RAR beta) and c ellular retinol-binding protein I, CRBPI, with Hoxb5 and c-ret in the gut m esoderm imply possible cooperation required for proper neuromuscular develo pment. To determine susceptibility and responsiveness of the developing gut and its neuromusculature to exogenous retinoids we used a mouse model of R A-induced caudal regression syndrome. The results showed that stage-specifi c RA treatment both in vivo and in vitro affected gut looping/rotation morp hogenesis and growth of asymmetrical structures such as the cecum together with delayed differentiation of the gut mesoderm and colonization of the po stcecal gut by neural crest-derived enteric neuronal precursors. These obse rvations demonstrate that RA has a direct effect on gut morphogenesis and i nnervation.