Zebrafish fgf3 and fgf8 Encode Redundant Functions Required for Otic Placode Induction

Abstract

Members of the fibroblast growth factor (FGF) family of peptide ligands have been implicated in otic placode induction in several vertebrate species. Here, we have functionally analyzed the roles of fgf3 and fgf8 in zebrafish otic development. The role of fgf8 was assessed by analyzing acerebellar (ace) mutants. fgf3 function was disrupted by injecting embryos with antisense morpholino oligomers (MO) specifically designed to block translation of fgf3 transcripts. Disruption of either fgf3 or fgf8 causes moderate reduction in the size of the otic vesicle. Injection of fgf3-MO into ace/ace mutants causes much more severe reduction or complete loss of otic tissue. Moreover, preplacode cells fail to express pax8 and pax2.1, indicating disruption of early stages of otic induction in fgf3-depleted ace/ace mutants. Both fgf3 and fgf8 are normally expressed in the germring by 50% epiboly and are induced in the primordium of rhombomere 4 by 80% epibloy. In addition, fgf3 is expressed during the latter half of gastrulation in the prechordal plate and paraxial cephalic mesendoderm, tissues that either pass beneath or persist near the prospective otic ectoderm. Conditions that alter the pattern of expression of fgf3 and/or fgf8 cause corresponding changes in otic induction. Loss of maternal and zygotic one-eyed pinhead (oep) does not alter expression of fgf3 or fgf8 in the hindbrain, but ablates mesendodermal sources of fgf signaling and delays otic induction by several hours. Conversely, treatment of wild-type embryos with retinoic acid greatly expands the periotic domains of expression of fgf3, fgf8, and pax8 and leads to formation of supernumerary and ectopic otic vesicles. These data support the hypothesis that fgf3 and fgf8 cooperate during the latter half of gastrulation to induce differentiation of otic placodes.

Constructing the hindbrain: Insights from the zebrafish

“…Early in development, ace/fgf8 is expressed in the germ ring, and before becoming restricted to the isthmus, ace/fgf8 is expressed throughout the anterior hindbrain, including in r4 where its expression overlaps with that of fgf3 (Reifers et al, 1998;Phillips et al, 2001; Fig. 5C).…”

Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti

“…At early stages of embryogenesis, Fgfr1, Fgfr2, and several FGFs, including FGF3, FGF8, FGF10, and FGF19, are critical for either the induction of the otic vesicle or the initial development of the sensory epithelium (Mansour et al, 1993;Ladher et al, 2000Ladher et al, , 2005Pirvola et al, 2000Pirvola et al, , 2002Phillips et al, 2001Phillips et al, , 2004Pauley et al, 2003;. At intermediate stages of development, FGF signaling is also important; tissuespecific deletion of Fgfr1 results in severe defects in the development of the auditory sensory epithelium apparently due to a severe reduction in the precursor cells that give rise to the organ of Corti.…”

Development of the zebrafish inner ear

“…In the zebrafish, this placode cavi- fgf8 (Reifers et al, 1998) Growth factor Small ear, abnormal neurogenesis (Adamska et al, 2000;Phillips et al, 2001) Targeted disruption (Sun et al, 1999) colourless (cls) sox10 (Dutton et al, 2001b) HMG box transcription factor…”