Neurogenetic asymmetries in the catshark developing habenulae: mechanistic and evolutionary implications

Abstract

Analysis of the establishment of epithalamic asymmetry in two non-conventional model organisms, a cartilaginous fsh and a lamprey, has suggested that an essential role of Nodal signalling, likely to be ancestral in vertebrates, may have been largely lost in zebrafsh. In order to decipher the cellular mechanisms underlying this divergence, we have characterised neurogenetic asymmetries during habenular development in the catshark Scyliorhinus canicula and addressed the mechanism involved in this process. As in zebrafsh, neuronal diferentiation starts earlier on the left side in the catshark habenulae, suggesting the conservation of a temporal regulation of neurogenesis. At later stages, marked, Alk4/5/7 dependent, size asymmetries having no clear counterparts in zebrafsh also develop in neural progenitor territories, with a larger size of the proliferative, pseudostratifed neuroepithelium, in the right habenula relative to the left one, but a higher cell number on the left of a more lateral, later formed population of neural progenitors. These data show that mechanisms resulting in an asymmetric, preferential maintenance of neural progenitors act both in the left and the right habenulae, on diferent cell populations. Such mechanisms may provide a substrate for quantitative variations accounting for the variability in size and laterality of habenular asymmetries across vertebrates.