The hypothalamus is an evolutionarily ancient brain region that regulates many innate behaviors, but its development is still poorly understood. To identify molecular mechanisms controlling hypothalamic specification and patterning, we used single-cell RNA-Seq to profile multiple stages of early hypothalamic development in the chick. We observe that hypothalamic neuroepithelial cells are initially induced from prethalamic-like cells. Two distinct hypothalamic progenitor populations emerge later, which give rise to paraventricular/mammillary and tuberal hypothalamus, respectively. At later developmental stages, the regional organization of the chick and mouse hypothalamus closely resembles one another. This study identifies selective markers for major subdivisions of the developing chick hypothalamus and many uncharacterized candidate regulators of hypothalamic patterning and neurogenesis. As proof of concept for the utility of the dataset, we demonstrate that prethalamic progenitor-derived follistatin inhibits hypothalamic induction. This study both clarifies the organization of the early developing hypothalamus and identifies novel molecular mechanisms controlling hypothalamic induction, regionalization, and neurogenesis.
Single-cell analysis of early chick hypothalamic development reveals that hypothalamic cells are induced from prethalamic-like progenitors.