Abstract
The adult hypothalamus is subdivided into distinct domains: pre‐optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views of hypothalamic development, which traditionally have attempted to map adult domains to correspondingly located embryonic domains. Instead, new studies indicate that hypothalamic neurones arise from progenitor cells that undergo anisotropic growth, expanding to a greater extent than other progenitors, and grow in different dimensions. We describe in particular how a multipotent Shh / Fgf10‐expressing progenitor population gives rise to progenitors throughout the basal hypothalamus that grow anisotropically and sequentially: first, a subset displaced rostrally give rise to anterior‐ventral/tuberal neuronal progenitors; then a subset displaced caudally give rise to mammillary neuronal progenitors; and, finally, a subset(s) displaced ventrally give rise to tuberal infundibular glial progenitors. As this occurs, stable populations of Shh +ive and Fgf10 +ive progenitors form. We describe current understanding of the mechanisms that induce Shh +ive /Fgf10 +ive progenitors and begin to direct their differentiation to anterior‐ventral/tuberal neuronal progenitors, mammillary neuronal progenitors and tuberal infundibular progenitors. Taken together, these studies suggest a new model for hypothalamic development that we term the “anisotropic growth model”. We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.
Highlights
The hypothalamus is an evolutionarily-ancient part of the ventral forebrain
Its overall organisation and resident cell types have been highly conserved in eukaryotes,[1] reflecting the crucial role of the hypothalamus to life
Genes Dev. Zhao T Szabo N Ma J Luo L Zhou X A varez Bo ado G Genetic mapping of Foxb1-cell lineage shows migration from caudal diencephalon to telencephalon and lateral hypothalamus
Summary
FIGURE Prechorda mesendoderm induces rostra diencepha ic ventra mid ine RDVM basa hypotha amic bHyp ce s Schematic sagitta views of chick embryo somites A Induction of Shh+ive RDVM ce s in the somite embryo through Shh Noda from under ying prechorda mesendoderm PM prechorda mesendoderm B Estab ishment of dorso ventra pattern through a Shh morphogen gradient from RDVM ce s inset shows patterned progenitor domains C Differentiation to bHyp ce s that co express Shh, BMP7 and Fgf[10] The return to cell cycle and proliferation that drives the development and growth of the basal hypothalamus occurs as the bHyp domain resolves into two Fgf10+ive progenitor subtypes: a posterior population that expresses Fgf[10] and BMP7 Figure A red and an anterior population that expresses Fgf[10] and Shh Figure A po ka dots These give rise to progenitor cells that down-regulate Fgf[10] but retain up regu ate Shh and are disp aced migrate anterior y Figure A hatched). This highlights the importance of future lineage-tracing studies in determining the origin of individual hypothalamic neuronal classes in discrete nuclei
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
