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Updated: Jan 11, 2026
09:25
Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
Published on: May 8, 2020
11.2K
Integrated ERK-PKA-YAP/TAZ-SHH Signaling Orchestrates Cortical Radial Glia Identity and Lineage Diversification
Zhuangzhi Zhang1, Zhejun Xu1, Tongye Fu1
1State Key Laboratory of Brain Function and Disorders, Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science, and Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 12, 2025
Summary
ERK and PKA signaling preserve neural stem cell neurogenic capacity by suppressing gliogenic pathways. This conserved mechanism in human brain development enhances self-renewal and extends neurogenesis, potentially driving evolutionary expansion.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Signaling pathways controlling cortical neurogenesis and gliogenesis are known.
- Integration of these pathways in radial glia (RG) lineage progression is unclear.
Purpose of the Study:
- Investigate how ERK/PKA, YAP/TAZ, and SHH signaling pathways interact.
- Determine their role in regulating cortical radial glia (RG) lineage progression and neurogenesis versus gliogenesis.
Main Methods:
- Utilized mouse genetic models to study signaling pathway functions.
- Reanalyzed published human cortical single-cell RNA sequencing (scRNA-seq) data.
Main Results:
- ERK and PKA signaling suppress YAP/TAZ and SHH pathways, preserving RG neurogenic capacity.
- YAP/TAZ signaling promotes ependymal fate; SHH signaling generates intermediate progenitors.
- Human cortical outer RGs show dominant ERK/PKA signaling, enhancing self-renewal and neurogenesis.
Conclusions:
- A tripartite network of ERK/PKA, YAP/TAZ, and SHH signaling coordinates neurogenesis and gliogenesis.
- This cross-repressive logic may underlie evolutionary expansion of the cortex.
- Identified a framework for understanding cortical development and evolution.
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