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Description:
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The vertebrate inner ear is a sensory organ responsible for auditory and vestibular
function . Since its complex structure and cell types arise from a simply structured group
of ectodermal cells , called the otic placode , the development of the inner ear has been a
popular subject in embryology and developmental biology for decades . To date , many
regulatory molecules and their functions have been identified in inner ear development
showing considerable conservation among vertebrates . In vertebrates , Fgfs (fibroblast
growth factors ) from surrounding tissues are the main otic inducer and regulate various
otic genes expression . Under the control of Fgf signals , pax2 /5 /8 genes are expressed in
the otic region in the critical stages of otic development suggesting their function in otic
development . In order to understand the function of pax2 /5 /8 genes and their
interactions in the developing ear , we utilize zebrafish as a model system . Among
zebrafish pax2 /5 /8 genes , pax8 is the earliest gene expressed in the preotic region while
pax2a and pax2b are expressed slightly later . We found that pax8 is initially required
for normal otic induction . Subsequently , pax8 , pax2a and pax2b function redundantly to maintain otic fate . After otic placodes are induced by an Fgf signaling network ,
expression of Fgf3 , one of otic inducers in zebrafish , persists in the hindbrain
rhombomere 4 . To investigate the function of the persistant Fgf3 expression , we
examined a mutant with expanded Fgf3 expression in the hindbrain . Together with fgf3
knockdown results , we discovered that Fgf3 has later roles in specifying the anteroposterior
(A -P ) axis in the otic vesicle and regulating hair cell formation . We further
identified pax5 as one of the genes regulated by the hindbrain Fgf3 activity , and pax5
function to be required for utricular hair cell survival . |