Populational heterogeneity and partial migratory origin of the ventromedial hypothalamic nucleus: genoarchitectonic analysis in the mouse

Abstract

The ventromedial hypothalamic nucleus (VMH) is one of the most distinctive hypothalamic tuberal structures, subject of numerous classic and modern functional studies. Commonly, the adult VMH has been divided in several portions, attending to differences in cell aggregation, cell type, connectivity, and function. Consensus VMH partitions in the literature comprise the dorsomedial (VMHdm), and ventrolateral (VMHvl) subnuclei, which are separated by an intermediate or central (VMHc) population (topographic names based on the columnar axis). However, some recent transcriptome analyses have identified a higher number of different cell types in the VMH, suggesting additional subdivisions, as well as the possibility of separate origins. We offer a topologic and genoarchitectonic developmental study of the mouse VMH complex using the prosomeric axis as a reference. We analyzed genes labeling specific VMH subpopulations, with particular focus upon the Nkx2.2 transcription factor, a marker of the alar-basal boundary territory of the prosencephalon, from where some cells seem to migrate dorsoventrally into VMH. We also identified separate neuroepithelial origins of a Nr2f1-positive subpopulation, and a new Six3-positive component, as well as subtle differences in origin of Nr5a1 positive versus Nkx2.2-positive cell populations entering dorsoventrally the VMH. Several of these migrating cell types are born in the dorsal tuberal domain and translocate ventralwards to reach the intermediate tuberal domain, where the adult VMH mass is located in the adult. This work provides a more detailed area map on the intrinsic organization of the postmigratory VMH complex, helpful for deeper functional studies of this basal hypothalamic entity.