Experiment Id | GSE240381 | Name | The ERK signaling drives evolutionary expansion of the mammalian cerebral cortex |
Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
Source | GEO | Curation Date | 2024-11-06 |
description | The molecular basis for cortical expansion during evolution remains largely unknown. Here, we found that FGF-ERK signaling promotes the self-renewal and expansion of cortical radial glial (RG) cells. Furthermore, FGF-ERK signaling induces Bmp7 expression in cortical RG cells, which increases the length of the neurogenic period. We demonstrate that ERK signaling and SHH signaling mutually inhibit each other in cortical RG cells. We also provide evidence that ERK signaling is elevated in cortical RG cells during development and evolution. We conclude that the evolutionary expansion of the human cortex is driven by ERK-BMP7-GLI3R signaling pathway in cortical RG cells, which participates in a positive feedback loop through antagonizing SHH signaling. We also propose that the molecular basis for cortical evolutionary dwarfism, exemplified by the lissencephalic mouse which originated from a larger and gyrencephalic ancestor, is due to mouse cortical RG cells receiving higher SHH signaling that antagonizes ERK signaling. The whole mouse cortex at E14.5 was dissected out under a microscope for scRNA-Seq analysis and bulk RNA-Seq analysis. Briefly, mouse embryos were dissected out and immediately submerged in fresh ice-cold Hanks balanced salt solution (Gibco 12175-095). The cortex was then cut into pieces and dissociated into a single-cell suspension using a Papain Cell Dissociation Kit (Miltenyi Biotec, catalog no. 130-092-628) according to the manufacturer's instructions. |