THE ROLE OF FGF-3 IN EARLY INNER-EAR DEVELOPMENT - AN ANALYSIS IN NORMAL AND KREISLER MUTANT MICE

The development of the otic placode is believed to depend on an induct ive signal from the adjacent hindbrain. A candidate for this signal is FGF-3 (Int-2), which is expressed in the hindbrain adjacent to the fu ture ear in rhombomeres 5 and 6 (r5 and r6). However, in vitro tests ( Represa et al. (1991), Nature 353, 561-563) conflict with findings fro m FGF-3 knockout mice (Mansour et al. (1993), Development 117, 13-28). The former suggest that FGF-3 from the hindbrain is required to induc e formation of the otocyst, while the latter imply that FGF-3 is requi red only in the later process of otocyst differentiation. We find that in normal embryos at early stages the gene is expressed not only in r 5 and rb, but also in most of the hindbrain anterior to this and in th e head ectoderm in the prospective otic placode region. In kreisler mu tant embryos, however, there is no heightened expression in r5 and r6, but the early patch of expression in the prospective otic placode ect oderm is still seen and the otic vesicle still forms at nearly the nor mal place. Subsequent malformations of the inner ear in kreisler and i n FGF-3 knockout mice are similar, involving failure of the developmen t of the endolymphatic appendage. These findings argue that FGF-3 is n ot required as an inductive signal for invagination of the otic placod e to form a vesicle, whose future site is already marked out independe ntly of any localized FGF-3 signal from r5 and r6. FGF-3 does, however , appear to be required for a correct pattern of differentiation withi n the vesicle. (C) 1996 Academic Press, Inc.