A. Karis et al., Transcription factor GATA-3 alters pathway selection of olivocochlear neurons and affects morphogenesis of the ear, J COMP NEUR, 429(4), 2001, pp. 615-630
Patterning the vertebrate ear requires the coordinated expression of genes
that are involved in morphogenesis, neurogenesis, and hair cell formation.
The zinc finger gene GATA-3 is expressed both in the inner ear and in affer
ent and efferent auditory neurons. Specifically, GATA-3 is expressed in a p
opulation of neurons in rhombomere 4 that extend their axons across the flo
or plate of rhombomere 4 (r4) at embryonic day 10 (E10) and reach the senso
ry epithelia of the ear by E13.5. The distribution of their cell bodies cor
responds to that of the cell bodies of the cochlear and vestibular efferent
neurons as revealed by labeling with tracers. Both GATA-3 heterozygous and
GATA-3 null mutant mice show unusual axonal projections, such as misrouted
crossing fibers and fibers in the facial nerve, that are absent in wild-ty
pe littermates. This suggests that GATA-3 is involved in the pathfinding of
efferent neuron axons that navigate to the ear. In the ear, GATA-3 is expr
essed inside the otocyst and the surrounding periotic mesenchyme. The latte
r expression is in areas of branching of the developing ear leading to the
formation of semicircular canals. Ears of GATA-3 null mutants remain cystic
, with a single extension of the endolymphatic duct and no formation of sem
icircular canals or saccular and utricular recesses. Thus, both the distrib
ution of GATA-3 and the effects of null mutations on the ear suggest involv
ement of GATA-3 in morphogenesis of the ear. This study shows for the first
time that a zinc finger factor is involved in axonal navigation of the inn
er ear efferent neurons and, simultaneously, in the morphogenesis of the in
ner ear. J. Comp. Neurol. 429:615-630, 2001. (C) 2001 Wiley-Liss, Inc.