GATA3 and NeuroD distinguish auditory and vestibular neurons during development of the mammalian inner ear

Abstract

The function of the zinc finger transcription factor GATA3 was studied in a newly established, conditionally immortal cell line derived to represent auditory sensory neuroblasts migrating from the mouse otic vesicle at embryonic day E10.5. The cell line, US/VOT-33, expressed GATA3, the bHLH transcription factor NeuroD and the POU-domain transcription factor Brn3a, as do auditory neuroblasts in vivo. When GATA3 was knocked down reversibly with antisense oligonucleotides, NeuroD was reversibly down-regulated. Auditory and vestibular neurons form from neuroblasts that express NeuroD and that migrate from the antero-ventral, otic epithelium at E9.5-10.5. On the medial side, neuroblasts and epithelial cells express GATA3 but on the lateral side they do not. At E13.5 most auditory neurons express GATA3 but no longer express NeuroD, whereas vestibular neurons express NeuroD but not GATA3. Neuroblasts expressing NeuroD and GATA3 were located in the ventral, otic epithelium, the adjacent mesenchyme and the developing auditory ganglion. The results suggest that auditory and vestibular neurons arise from different, otic epithelial domains and that they gain their identity prior to migration. In auditory neuroblasts, NeuroD appears to be dependent on the expression of GATA3.

Hedgehog Signaling Governs the Development of Otic Sensory Epithelium and Its Associated Innervation in Zebrafish

“…External cues such as Hh, may regulate within the otic epithelium the restricted expression of one (or a combination of) transcription factor(s), that direct neuronal identity upstream of ngn1. In mouse, GATA3 expression in the early otic epithelium is spatially and temporally restricted to the neurogenic territory responsible for the production of cochlear neurons, and later on selectively marks the cochlear part of the CVG (Karis et al, 2001;Lawoko-Kerali et al, 2004;Koundakjian et al, 2007). Our study showed that in the zebrafish, gata3 expression domain overlaps only partially with the otic neurogenic domain.…”

Sonic hedgehog and retinoic acid synergistically promote sensory fate specification from bone marrow-derived pluripotent stem cells

“…In contrast, substantial increases in Irx2 (4,000-fold) and Sox10 (400-fold), both of which are expressed in vestibulocochlear ganglia (VCG), trigeminal ganglia (TG), and dorsal root ganglia during development (14-17), were detected in MSCs grown for 7 days in the presence of Shh and RA together. In addition, GATA3, a zinc finger transcription factor expressed in VCG and TG (18)(19)(20), and P2X3, a sensory neuron-specific ionotropic purine receptor (21), were up-regulated 300-and 200-fold, respectively, in the presence of Shh and RA. However, Ret, a glial cell-line-derived neurotrophic factor coreceptor expressed in all sensory ganglia except VCG, was downregulated during neuronal differentiation.…”

Coordinated regulation of gene expression by Brn3a in developing sensory ganglia

“…GATA3 has a known role in the development of motor neurons originating in rhombomere 4, which innervate the inner ear, and the inner ear itself (Karis et al, 2001). NeuroD1 is also required for normal development of the sensory neurons of the inner ear (Liu et al, 2000), and may have a cross-regulatory relationship with GATA3 (Lawoko-Kerali et al, 2004). Although the role of the Irx genes in sensory development has not been described in mice, the zebrafish protein iro7, a possible paralogue of Irx1, is required for trigeminal placode development in fish (Itoh et al, 2002).…”