Colombo A, Palma K, Armijo L, Mione M, Signore IA, Morales C, Guerrero N, Pérez R, Suazo J, Marcelain K, Briones L, Härtel S, Wilson SW, and M Concha
Development, 140, 3997-4007

Although progress has been made in resolving the genetic pathways that mediate the development of habenular asymmetry, little is known about the genes that interpret this information and mediate the development of structural asymmetries between neurons on left and right. In this study we identify daam1 as a new asymmetric component of the signalling pathways leading to asymmetric habenular morphogenesis. The extent of Daam1 expression in habenular neuron dendrites mirrors the asymmetric growth of habenular neuropil between left and right. Local loss and gain of Daam1 function in the left Hb does not affect cell number nor subtype organisation but leads to a decrease or increase of neuropil, respectively. Daam1 consequently plays a key role in the asymmetric growth of habenular neuropil downstream of the pathways that specify asymmetric cellular domains in the Hb. Furthermore, Daam1 also mediates the development of habenular efferent connectivity as local loss and gain of Daam1 function leads to impaired or enhanced growth of habenular neuron terminals in the interpeduncular nucleus, respectively. At the level of single habenular neurons, abrogation of Daam1 disrupts the growth of both dendritic and axonal processes. Knockdown of Daam1 results in disorganised filamentous actin and α-tubulin in the Hb, a phenotype that can be rescued by concomitant overexpression of human Daam1 mRNA. Our results indicate that Daam1 works as an effector of asymmetric morphogenesis through mediating the growth of dendritic and axonal processes of dorsal habenular neurons.