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Cortical neural stem and progenitor cells

The development of the neocortex, particularly its distinct morphology, largely depends on the activity and behavior of cortical neural stem and progenitor cells (cNPCs). These cells generate the majority of neurons in the adult neocortex during a specific phase of cortical development known as neurogenesis. The number of neurons is a critical determinant of the neocortex's appearance: the greater the number of neurons formed, the larger and more convoluted the neocortex becomes. The number of neurons is closely linked to the activity and behavior of cNPCs. Therefore, the regulation of the activity and behavior of these cNPCs forms a crucial basis for the morphology of the neocortex, and changes in this regulation can lead to morphological differences.

 

Regulation of progenitor cells

The regulation of cNPCs occurs via genes that are specifically expressed in these cells and not, for example, in neurons. We are interested in precisely those genes that are specifically expressed in cNPCs but are differentially active between different primate species. These genes are most likely responsible for the different behavior of cNPCs and thus for the different morphology of the neocortex between different primate species. Transcription factors play a central role here, as they regulate the expression of several genes and thus changes in these transcription factors can have a strong influence on the behavior and activity of cNPCs.

Zinc finger transcription factors

A family of transcription factors, the so-called zinc finger transcription factors (ZNFs), has expanded considerably, particularly in primates. ZNFs are negative regulators of transcription defined by the so-called zinc finger domain, which allows them to bind to specific DNA sequences. Many of these ZNFs have been proposed to play important roles in neural development and in the development of brain malformations. Given the expansion of ZNFs in primates and their potential contribution to neural development and brain malformations, we consider these transcription factors as important candidates for the regulation of different neocortex morphology within the primate order.