The hypothalamus is the central regulator of vital physiological homeostasis and behavior in mammalian. In contrast to the cortex that is organized in a columnar structure, hypothalamic neurons form multiple functional nuclei arrayed in a three-dimensional structure to regulate behavior.

A research team led by Prof. WANG Xiaoqun from the Institute of Biophysics (IBP) of the Chinese Academy of Sciences found that both radial glial cells (RG) and outer raial glial cells (oRG) cells are primary progenitor cells during cortical development.

Molecular features of distinct cortical progenitors and their contribution to evolutionary expansion of cerebral cortex have been profiled. However, mechanisms of hypothalamus development remain unclear.

Recently, WANG's group has revealed cellular and molecular properties of neural progenitors in developing mammalian hypothalamus. The study was published in Nature Communications on August 13.

The researchers found that hypothalamic radial glial (hRG) and hypothalamic mantle zone radial glial (hmRG) cells were neural progenitors in the developing mammalian hypothalamus. The hmRG cells originated from hRG cells and produce neurons.

"During the early development of hypothalamus, neurogenesis occured in radial columns and was initiated from hRG cells. The radial glial fibers were oriented toward the locations of hypothalamic subregions which acted as a scaffold for neuronal migration," said Prof. WANG.

Using single-cell RNA sequencing, the researchers revealed progenitor subtypes in human developing hypothalamus and characterized specific progenitor genes. They demonstrated that HMGA2 was involved in E2F1 pathway, regulating the proliferation of progenitor cells. Different neuronal subtypes started to differentiate and expressed specific genes of hypothalamic nucleus at gestational week 10.

Moreover, researchers revealed the developmental conservation of nuclear structures and marker genes in mouse and human hypothalamus. These data provided a basic understanding of neurogenesis and regional formation of the non-laminated hypothalamus.

This work was supported by the National Basic Research Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, the National Natural Science Foundation of China, and Beijing Brain Initiative of Beijing Municipal Science & Technology Commission.