Temporal and spatial regulation of alpha6 integrin expression during the development of the cochlear-vestibular ganglion

Abstract

The neurons of the cochlear-vestibular ganglion (CVG) that innervate the sensory hair cells of the inner ear are derived from the otic epithelium early in development. Neuroblasts detach from neighboring cells, migrate into the mesenchyme where they coalesce to form the ganglion complex, then send processes back into the epithelium. Cell migration and neuronal process formation involve changes in cellular interactions with other cells and proteins in the extracellular matrix that are orchestrated by cell surface-expressed adhesion molecules, including the integrins. I studied the expression pattern of the alpha6 integrin subunit during the early development of the CVG using immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) in murine tissue sections, otocyst, and ganglion explants. At embryonic day (E)10.5 alpha6 integrin was expressed in the otic epithelium but not in migrating neuroblasts. Importantly, the loss of alpha6 was associated with exit from the epithelium, not neuronal determination, revealing differentiation cues acutely associated with the cellular environment. Markers of glial and neuronal phenotype showed that alpha6-expressing cells present in the CVG at this stage were glia of neural crest origin. By E12.5 alpha6 expression in the ganglion increased alongside the elaboration of neuronal processes. Immunohistochemistry applied to otocyst cultures in the absence of glia revealed that neuronal processes remained alpha6-negative at this developmental stage and confirmed that alpha6 was expressed by closely apposed glia. The spatiotemporal modulation of alpha6 expression suggests changing roles for this integrin during the early development of inner ear innervation.