Excessive feedback of Cyp26a1 promotes cell non-autonomous loss of retinoic acid signaling.

ABSTRACT: Teratogenic levels of retinoic acid (RA) signaling can cause seemingly contradictory phenotypes indicative of both increases and decreases of RA signaling. However, the mechanisms underlying these contradictory phenotypes are not completely understood. Here, we report that using a hyperactive RA receptor to enhance RA signaling in zebrafish embryos leads to defects associated with gain and loss of RA signaling. While the gain-of-function phenotypes arise from an initial increase in RA signaling, using genetic epistasis analysis we found that the loss-of-function phenotypes result from a clearing of embryonic RA that requires a rapid and dramatic increase in cyp26a1 expression. Thus, the sensitivity of cyp26a1 expression to increased RA signaling causes an overcompensation of negative feedb

SUBMITTER: Rydeen A 

PROVIDER: S-EPMC4529768 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature