Genetic signal pathways that control the development of the vestibular system and clinical correlates in patients with balance disorders

This review of vestibular development in mammals presents the sequence of developmental events correlated with the patterns of gene expressions and when possible their interactions with downstream target genes that must act in a coordinated fashion to produce mature, functional balance receptors. Specification of the early otic anlage by patterning genes is first addressed. This is followed by the genetic control of the pars superior portion of the otic anlage that sets the pattern for the formation of the three semicircular ducts and their associated cristae. The genes that control the formation of the sensory maculae of the utricle and saccule are discussed next followed by a review of the genes involved in the formation of the acellular membranes that are associated with the cristae and maculae of the vestibular labyrinth. In the utricle and saccule these acellular matrices have associated calcium carbonate crystals with protein components known as otoconia whose formation is controlled by a series of related genes. A series of expressed genes are involved in the determination of both sensory hair cells that populate the vestibular sensory epithelia and sensory neurons located within Scarpa's ganglion that act as primary afferent connections between the vestibule's sensory hair cells and the central nervous system's pathways of balance. The last section of this chapter contains a discussion of the genetic involvement of some of these genes that influence the development of the peripheral vestibular receptors in the etiology of human balance disorders.