13-P015 N-cadherin mediates aggregation of placode-derived cranial sensory neurons and is regulated by Slit1-Robo2 signaling

ulate the transition between self-renewal and differentiation stage in different systems, and both are associated with the maintenance of the progenitor state. The general question that arises is how those signals are integrated within otic progenitors so that they result in a precise cell diversification. We have studied the interactions between Sox2 and Notch pathways in otic neurosensory progenitors. Experiments combined electroporation of c-Sox2 and hJag1 with in vitro explants, qRT-PCR and in situ hybridisation analysis. The results show that: (1) Sox2 and Ser1 are co-expressed in neurosensory otic progenitors, throughout inner ear development. (2) Forced expression of hJag1 was able to extend the domain of Sox2 expression in a nonautonomous manner, the effect being Notch-dependent. On the contrary, Sox2 did not affect Ser1 expression. (3) hJag1 activated the Notch pathway and induced typical Notch targets, including Hey1 and Hes1. (4) c-Sox2 overexpression resulted the up-regulation of Notch targets, particularly Hey1. The Sox2-induced Hey1 up-regulation was Notch-dependent, as shown by its blockade by DAPT. Taken together, the results suggest that there is a cooperation between Sox and Notch pathways in the maintenance of the commitment and self-renewal state of the proneural domain. Supported by MCINN, Spain and FCT, Portugal.