Spatial and temporal segregation of auditory and vestibular neurons in the otic placode

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.07.011 Byline: Donald Bell (a), Andrea Streit (a), Itziar Gorospe (b), Isabel Varela-Nieto (b), Berta Alsina (c), Fernando Giraldez (c) Keywords: Chick; Cochlear-vestibular ganglion; Ear development; Neuroblast; Neurogenesis; Otic vesicle; Proneural genes; Sensory precursors; Temporal specification Abstract: The otic placode generates the auditory and vestibular sense organs and their afferent neurons; however, how auditory and vestibular fates are specified is unknown. We have generated a fate map of the otic placode and show that precursors for vestibular and auditory cells are regionally segregated in the otic epithelium. The anterior-lateral portion of the otic placode generates vestibular neurons, whereas the posterior-medial region gives rise to auditory neurons. Precursors for vestibular and auditory sense organs show the same distribution. Thus, different regions of the otic placode correspond to particular sense organs and their innervating neurons. Neurons from contiguous domains rarely intermingle suggesting that the regional organisation of the otic placode dictates positional cues to otic neurons. But, in addition, vestibular and cochlear neurogenesis also follows a stereotyped temporal pattern. Precursors from the anterior-lateral otic placode delaminate earlier than those from its medial-posterior portion. The expression of the proneural genes NeuroM and NeuroD reflects the sequence of neuroblast formation and differentiation. Both genes are transiently expressed in vestibular and then in cochlear neuroblasts, while differentiated neurons express Islet1, Tuj1 and TrkC, but not NeuroM or NeuroD. Together, our results indicate that the position of precursors within the otic placode confers identity to sensory organs and to the corresponding otic neurons. In addition, positional information is integrated with temporal cues that coordinate neurogenesis and sensory differentiation. Author Affiliation: (a) Department of Craniofacial Development, King's College London, London SE1 9RT, UK (b) Instituto de Investigaciones Biomedicas 'Alberto Sols', (CSIC-UAM) CIBER-ER, c/Arturo Duperier 4, 28029 Madrid, Spain (c) CEXS, Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona (UPF-PRBB), Dr. Aiguader 88, 08001, Barcelona, Spain Article History: Received 6 June 2008; Revised 9 July 2008; Accepted 9 July 2008