Model for regulation of SAG development by Fgf.

<p>(A) Neuroblast specification at early stages. A moderate level of Fgf3 and Fgf8 in a gradient generated by the utricular macula specifies neuroblasts in the floor of the otic vesicle (step 1), and nascent neuroblasts quickly delaminate from the otic vesicle (step 2). (B) As development proceeds, neuroblasts establish a pool of transit-amplifying (TA) progenitors (step 3), which eventually differentiate into mature neurons and express Fgf5 (step 4). Rising levels of neuronal Fgf5, combined with Fgf3 and Fgf8 from the growing utricular macula, exceeds an upper threshold that serves to terminate specification of new neuroblasts within the otic vesicle. Neuronal Fgf5 also slows differentiation of progenitors into mature neurons. (C, D) At stages immediately following establishment of the transit-amplifying pool, experimental attenuation of Fgf signaling promotes maturation of neurons at the expense of progenitors (C) whereas elevating Fgf inhibits maturation, expanding the size of the transit-amplifying pool (D).