Shifting boundaries of retinoic acid activity control hindbrain segmental gene expression

摘要: Retinoic acid (RA) generated by Raldh2 in paraxial mesoderm is required for specification of the posterior hindbrain, including restriction Hoxb1 expression to presumptive rhombomere 4 (r4). requires 3' and 5' RA response elements widespread induction up r4 r3/r5 repression, but has previously been detected only from r5-r8, vHnf1 repression zebrafish. We demonstrate mouse embryos that an signal initially travels r3, forming a boundary next r2 domain Cyp26a1 (which encodes RA-degrading enzyme). After induction, quickly shifts r4/r5, coincident with Cyp26c1 r4. A functional role degradation was established through examination RA-treated embryos. Analysis Raldh2-/- vHnf1-/- supports direct r3/r5, as well indirect via r4/r5 boundary. Our findings suggest Cyp26 generate shifting boundaries activity, such r3-r4 receives short pulse r5-r8 long RA. These two pulses activity function establish on opposite sides