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

Area of Science:

• Developmental biology
• Neuroscience
• Genetics

Background:

• Neocortex expansion relies on basal progenitor (BP) proliferation, influenced by extracellular matrix (ECM) components and integrin signaling.
• The precise molecular mechanisms regulating BP proliferation and cell fate remain incompletely understood.

Purpose of the Study:

• To investigate the role of the transcription factor Sox9 in regulating basal progenitor proliferation and neocortical development.
• To determine if Sox9 influences extracellular matrix (ECM) production and cell-fate decisions in basal progenitors.

Main Methods:

• Analysis of Sox9 expression in mouse, human, and ferret basal progenitors.
• Conditional gene manipulation (Sox9 expression) in mouse basal progenitor lineage.
• Assessment of progenitor proliferation, cell fate markers (Tbr2, Olig2), and neuron production.

Main Results:

• Sox9 drives expression of ECM components, including laminin 211, which enhances BP proliferation in embryonic mouse neocortex.
• Sox9 is expressed in human and ferret BPs and is essential for their proliferation.
• Conditional Sox9 expression in mouse BPs increases proliferation, reduces Tbr2, induces Olig2 (suggesting premature gliogenesis), and stimulates non-autonomous BP proliferation and upper-layer neuron production.

Conclusions:

• Sox9 plays a crucial role in regulating basal progenitor proliferation, neuron production, and cell fate decisions (neurogenic vs. gliogenic).
• Sox9's influence on these processes suggests it may have been a key factor in the evolutionary expansion of the neocortex.