Zebrafish and medaka: model organisms for a comparative developmental approach of brain asymmetry

Abstract

Comparison between related species is a successful approach to uncover conserved and divergent principles of development. Here, we studied the pattern of epithalamic asymmetry in zebrafish (Danio rerio) and medaka (Oryzias latipes), two related teleost species with 115-200 Myr of independent evolution. We found that these species share a strikingly conserved overall pattern of asymmetry in the parapineal-habenular-interpeduncular system. Nodal signalling exhibits comparable spatial and temporal asymmetric expressions in the presumptive epithalamus preceding the development of morphological asymmetries. Neuroanatomical asymmetries consist of left-sided asymmetric positioning and connectivity of the parapineal organ, enlargement of neuropil in the left habenula compared with the right habenula and segregation of left-right habenular efferents along the dorsoventral axis of the interpeduncular nucleus. Despite the overall conservation of asymmetry, we observed heterotopic changes in the topology of parapineal efferent connectivity, heterochronic shifts in the timing of developmental events underlying the establishment of asymmetry and divergent degrees of canalization of embryo laterality. We offer new tools for developmental time comparison among species and propose, for each of these transformations, novel hypotheses of ontogenic mechanisms that explain interspecies variations that can be tested experimentally. Together, these findings highlight the usefulness of zebrafish and medaka as comparative models to study the developmental mechanisms of epithalamic asymmetry in vertebrates.

Description of Embryonic Development of Spotted Green Pufferfish (Tetraodon nigroviridis)

“…Therefore, it has been proposed that differences in the morphology and architecture of laterality organs might account for differences in the robustness of laterality between species. 20 It would be interesting to see if the same is true for tetraodon.…”

“…19 Signore et al found evidence for a higher degree of canalization (robustness) of laterality regarding epithalamic and heart looping asymmetries in medaka compared to zebrafish. 20 Notably, medaka has a relatively larger Kupffer's vesicle than zebrafish, which is also more similar to the mouse node. The Kupffer's vesicle of medaka contains an epithelial layer of ciliated cells only in the dorsal roof of the organ, whereas ciliated cells are found also in the ventral floor of the organ in zebrafish.…”

Nodal signalling and asymmetry of the nervous system

“…lizards, chick and rodents) (reviewed in [14]), and recent reports also extend this asymmetric feature to humans [15,16]. Asymmetries comprise the bilaterally paired habenular nuclei (Hb) and some midline components of the pineal complex, and show significant variations in morphology, and in the extent and sidedness of L-R differences among species [14,[17][18][19]. Importantly, developmental studies in fishes reveal that epithalamic asymmetry is preceded and controlled by the asymmetric expression of Nodal (figure 1c-e) [20][21][22] (see details below in §4).…”

“…Such intimate interaction between the Hb and PpO could have brought the PpO into the field of influence of asymmetric Nodal, which already was acting on the Hb, either by moving the PpO to the left or by modifying spatial or temporal aspects of PpO ontogeny ( figure 6d(iii)). Evidence that such a modification might have occurred comes from studies showing that the onset of PpO connectivity is heterochronic when comparing the ontogeny of epithalamic asymmetry among related teleost species [18,73]. The fact that in the lamprey the PpO only develops after asymmetries of the Hb are anatomically distinguishable [22] only argues against a possible direct control of Nodal on the asymmetric projection of the PpO in this species, but is coherent with the idea that this effect can be mediated by the asymmetry of the Hb.…”

The ancestral role of nodal signalling in breaking L/R symmetry in the vertebrate forebrain

“…Whether these mechanisms have been conserved throughout vertebrate evolution remains unclear. Asymmetric nodal expression in the forebrain, for instance, has only been reported in teleosts 10,15,16 . Analyses of habenular asymmetry establishment in agnathans (or cyclostomes) and cartilaginous fishes (or chondrichthyans) are of major interest to address this issue.…”