Ear Research:
Our
long term goal is to understand how cells are specified
to form the ear. In all vertebrates, the initial
morphological event in ear development is the formation
of the embryonic otic placode, a thickening of the
head ectoderm adjacent to the developing hindbrain.
Through interactions with adjacent tissues and incorporation
of additional cells from the neural crest and mesoderm,
the placode develops into the otic vesicle, also
called the otocyst, a differentiated structure with
sharply defined borders.
Later, the otic vesicle forms the inner ear including
its neurons and most
of its structural elements. A variety of studies
suggest that cells are specified to form the otic
placode in response to inductive signals from neighboring
tissues. However,
little is currently known about the sources or nature
of these signals or how cells respond to these putative
signals to form the otic placode.
Members of the Fgf family of growth factors and
the Dlx family of transcription factors have been
implicated in this signal-response pathway. Our studes
show that compromising Fgf3 and Fgf8 signaling blocks
ear development; only a few scattered otic cells
form. Removal of dlx3b, dlx4b and sox9a
genes together also blocks ear development, although
a few residual cells form an otic epithelium. These
cells fail to form if sox9b function is also blocked.
Combined loss of Fgf signaling and the three transcription
factor genes, dlx3b, dlx4b and sox9a, also completely
eliminates all indications of otic cells. Expression
of sox9a but not dlx3b, dlx4b or sox9b requires Fgf3
and Fgf8. Our results provide evidence for Fgf3-
and Fgf8-dependent and -independent genetic pathways
for otic specification and support the notion that
Fgf3 and Fgf8 function to induce both the otic placode
and the epithelial organization of the otic vesicle.
