The prefrontal cortex (PFC) is the cerebral cortex which covers the front part of the frontal lobe in mammalian brain anatomy and has increased six-fold throughout human evolution. This brain region has been implicated in planning complex cognitive behavior, decision-making and regulating social behavior.

Since disturbance or failure of PFC development may contribute to several cognitive deficits seen in patients with neurodevelopmental disorders, such as intellectual disability, autism spectrum disorders and schizophrenia, there is a need for detailed knowledge of the development of the PFC.

Prof. WANG Xiaoqun from the Institute of Biophysics of Chinese Academy of Sciences, together with researchers from Peking University and the Capital University of Medical Sciences and other collaborators, applied single-cell transcriptional profiling to identify cell types in the developing human PFC and distinguished their developmental features. The findings were published online in the journal Nature.

In this study, the researchers described the molecular features of cells in the PFC during human brain development at gestational weeks eight to 26. The data showed heterogeneity of neural progenitor cells that have the potential of proliferation and differentiation to neurons or to glial cells.

Intermediate progenitor (IP) cells, acting as transit amplifying progenitor cells, play a critical role in mammalian cerebral cortex development, allowing neurons to be generated at a tremendous speed in a short period. The researchers found new markers of IP cells and revealed the development feature of these cells.

They also illustrated the critical periods of the proliferation, migration and maturation of excitatory neurons.

In addition, the data indicated that there are a few of interneuron progenitor cells in the early period of PFC while they are inactively progressing through the cell cycle, implying interneurons may be generated locally in the developing human PFC.

The screening and characterization approach adopted by researchers provided a blueprint for understanding human PFC development in the early and mid-gestational stages with which to systematically dissect the cellular basis and molecular regulation of PFC function in humans. It is also a powerful tool for investigating the mechanisms behind neurological diseases related to abnormal structure or dysfunction of the PFC and exploring potential therapies.

This work was supported by National Basic Research Program of China, the Strategic Priority Research Program of the Chinese Academy of Sciences and the National Natural Science Foundation of China.