Role for retinoid signaling in left-right asymmetric digestive organ morphogenesis.
The looping events that establish left-right asymmetries in the vertebrate gut tube are poorly understood. Retinoic acid signaling is known to impact left-right development in multiple embryonic contexts, although its role in asymmetric digestive organ morphogenesis is unknown. Here, we show that the genes for retinaldehyde dehydrogenase (RALDH2) and a retinoic acid hydroxylase (CYP26A1) are expressed in complementary patterns in the Xenopus gut during looping. A late-stage chemical genetic assessment reveals that agonists and antagonists of retinoid signaling generate abnormal gut looping topologies, digestive organ heterotaxias, and intestinal malrotations. Accessory organ deformities commonly associated with intestinal malrotation in humans, such as annular pancreas, pancreas divisum, and extrahepatic biliary tree malformations, are also induced by distinct retinoid receptor agonists. Thus, late-stage retinoic acid signaling is likely to play a critical role in asymmetric gut tube morphogenesis and may underlie the etiology of several clinically relevant defects in the digestive system.
Lipscomb
Kristen
K
Natural Sciences Collegium, Eckerd College, St. Petersburg, Florida, USA.
Schmitt
Christopher
C
Sablyak
Amanda
A
Yoder
Jeffrey A
JA
Nascone-Yoder
Nanette
N
D000080924:Aldehyde Dehydrogenase 1 Family; D042931:Aldehyde Oxidase / Q000235:genetics; D000818:Animals; D019521:Body Patterning; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004064:Digestive System / Q000254:growth & development / Q000378:metabolism; D009024:Morphogenesis; D010088:Oxidoreductases / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D050697:Retinal Dehydrogenase; D000072516:Retinoic Acid 4-Hydroxylase; D012176:Retinoids / Q000378:metabolism*; D015398:Signal Transduction; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism
D018168:Receptors, Retinoic Acid; D012176:Retinoids; D029867:Xenopus Proteins; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D000072516:Retinoic Acid 4-Hydroxylase; D000080924:Aldehyde Dehydrogenase 1 Family; D050697:Retinal Dehydrogenase; C493756:aldh1a2 protein, Xenopus; D042931:Aldehyde Oxidase