Molecular mechanisms governing development of the hindbrain choroid plexus and auditory projection: A validation of the seminal observations of Wilhelm His.

Abstract

Studies by His from 1868 to 1904 delineated the critical role of the dorsal roof plate in the development of the hindbrain choroid plexus, and of the rhombic lips in the development of hindbrain auditory centers. Modern molecular studies have confirmed these observations and placed them in a mechanistic context. Expression of the transcription factor Lmx1a/b is crucial to the development of the hindbrain choroid plexus, and also regulates the expression of Atoh1, a transcription factor that is essential for the formation of the cochlear hair cells and auditory nuclei. By contrast, development of the vestibular hair cells, vestibular ganglion and vestibular nuclei does not depend on Lmx1a/b. These findings demonstrate a common dependence on a specific gene for the hindbrain choroid plexus and the primary auditory projection from hair cells to sensory neurons to hindbrain nuclei. Thus, His’ conclusions regarding the origins of specific hindbrain structures are borne out by molecular genetic experiments conducted more than a hundred years later.