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 signaling molecules for morphogenesis of vertebrate embryos. Little is known, however, about morphogenetic factors controlling the development of the gastrointestinal tract and RA is likely to be involved. In the mouse, teratogenic doses of RA cause truncation of the embryonic caudal body axis that parallel the caudal regression syndrome as described in humans. These changes are often associated with anomalies of the lower digestive tract. Overlapping spatiotemporal expression of retinoic acid receptor-beta (RAR beta) and cellular retinol-binding protein I, CRBPI, with Hoxb5 and c-ret in the gut mesoderm imply possible cooperation required for proper neuromuscular development. To determine susceptibility and responsiveness of the developing gut and its neuromusculature to exogenous retinoids we used a mouse model of RA-induced caudal regression syndrome. The results showed that stage-specific RA treatment both in vivo and in vitro affected gut looping/rotation morphogenesis and growth of asymmetrical structures such as the cecum together with delayed differentiation of the gut mesoderm and colonization of the postcecal gut by neural crest-derived enteric neuronal precursors. These observations demonstrate that RA has a direct effect on gut morphogenesis and innervation.
Pitera
J E
JE
Gastroenterology Unit, Institute of Child Health, University College of London, London, United Kingdom.
Smith
V V
VV
Woolf
A S
AS
Milla
P J
PJ
D000818:Animals; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects; D005260:Female; D007422:Intestines / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D009420:Nervous System / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D009924:Organ Culture Techniques; D011247:Pregnancy; D012447:Sacrum / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D013577:Syndrome; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage*
D014212:Tretinoin