Extracellular matrix-inducing Sox9 promotes both basal progenitor proliferation and gliogenesis in developing neocortex

eLife

Katherine R Long¹  Ayse Güven¹  Holger Brandl¹  Marta Florio¹  Wieland B Huttner¹  Denise Stenzel¹  Samir Vaid¹  Nereo Kalebic² 

[1] Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany;Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany;Human Technopole, Milan, Italy;

关键词: mouse;    ferret;    human;    Human;    Mouse;   

DOI  :  10.7554/eLife.49808

来源: publisher

【 摘 要 】

Neocortex expansion is largely based on the proliferative capacity of basal progenitors (BPs), which is increased by extracellular matrix (ECM) components via integrin signaling. Here we show that the transcription factor Sox9 drives expression of ECM components and that laminin 211 increases BP proliferation in embryonic mouse neocortex. We show that Sox9 is expressed in human and ferret BPs and is required for BP proliferation in embryonic ferret neocortex. Conditional Sox9 expression in the mouse BP lineage, where it normally is not expressed, increases BP proliferation, reduces Tbr2 levels and induces Olig2 expression, indicative of premature gliogenesis. Conditional Sox9 expression also results in cell-non-autonomous stimulation of BP proliferation followed by increased upper-layer neuron production. Our findings demonstrate that Sox9 exerts concerted effects on transcription, BP proliferation, neuron production, and neurogenic vs. gliogenic BP cell fate, suggesting that Sox9 may have contributed to promote neocortical expansion.

【 授权许可】

CC BY