Daam1a mediates asymmetric habenular morphogenesis by regulating dendritic and axonal outgrowth

Abstract

Although progress has been made in resolving the genetic pathways that specify neuronal asymmetries in the brain, little is known about genes that mediate the development of structural asymmetries between neurons on left and right. In this study, we identify daam1a as an asymmetric component of the signalling pathways leading to asymmetric morphogenesis of the habenulae in zebrafish. Daam1a is a member of the Formin family of actin-binding proteins and the extent of Daam1a expression in habenular neuron dendrites mirrors the asymmetric growth of habenular neuropil between left and right. Local loss and gain of Daam1a function affects neither cell number nor subtype organisation but leads to a decrease or increase of neuropil, respectively. Daam1a therefore plays a key role in the asymmetric growth of habenular neuropil downstream of the pathways that specify asymmetric cellular domains in the habenulae. In addition, Daam1a mediates the development of habenular efferent connectivity as local loss and gain of Daam1a function impairs or enhances, respectively, the growth of habenular neuron terminals in the interpeduncular nucleus. Abrogation of Daam1a disrupts the growth of both dendritic and axonal processes and results in disorganised filamentous actin and α-tubulin. Our results indicate that Daam1a plays a key role in asymmetric habenular morphogenesis mediating the growth of dendritic and axonal processes in dorsal habenular neurons.

Formins as effector proteins of Rho GTPases

“…These animals die during embryonic development or at early postnatal days 80 . The role of Daam1 in the nervous system has been analyzed in zebrafish 81 . Here, Daam1 is enriched in the dorsal part of the asymmetric habenular neuropil.…”

“…Loss of Daam1 in zebrafish embryos resulted in disturbed asymmetry and reduced neuropil formation. This can be explained by the finding that Daam1 regulates outgrowth of neuronal axons and dendrites 81 . Another Daam1-dependent process is the closure of the neural tube during embryogenesis.…”

Asymmetry of the Brain: Development and Implications

“…Various asymmetrically expressed factors, such as Kctd12.1, Kctd12.2, and Daam1a (dishevel associated activator of morphogenesis), have been associated with the growth of habenular neuropils while not apparently being required for the specification of habenular neuronal subtypes (30,157) (Table 1). In addition to dendritic extensions from habenular neurons, these neuropil domains contain afferent connections from pp cells to the left habenula (33) and from a subset of mitral cells of the olfactory bulb to the right habenula (74,116).…”

Daam1 regulates fascin for actin assembly in mouse oocyte meiosis

“…29 In addition, abrogation of Daam1 resulted in disorganized filamentous actin and a-tubulin in habenula. 30 Thus, our results suggested that Daam1 might play conserved roles between difference species or cell types, and positively affect actin assembly, followed by disrupted polar body extrusion in mouse oocytes.…”