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Differentiation of Mouse Embryonic Stem Cells into Cortical Interneuron Precursors
Published on: December 3, 2017
SOX6 controls dorsal progenitor identity and interneuron diversity during neocortical development
Eiman Azim1, Denis Jabaudon, Ryann M Fame
1Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair, Harvard Medical School, Boston, Massachusetts, USA.
Nature Neuroscience
|August 7, 2009
Summary
The transcription factor SOX6 regulates brain development by controlling the segregation of dorsal and ventral cell types. Loss of SOX6 impacts progenitor identity and the diversity of cortical interneurons.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Neuronal diversity in the central nervous system (CNS) arises from the precise spatial and temporal regulation of molecular factors.
- Understanding the genetic mechanisms governing progenitor identity and neuronal differentiation is crucial for comprehending brain development.
Purpose of the Study:
- To investigate the role of the transcription factor SOX6 in regulating forebrain progenitor identity and cortical interneuron development.
- To elucidate how SOX6 controls the molecular segregation between dorsal (pallial) and ventral (subpallial) telencephalic progenitors.
Main Methods:
- Utilized mouse models to study gene expression patterns during corticogenesis.
- Analyzed the effects of SOX6 loss-of-function on progenitor identity and interneuron differentiation.
- Examined the mutually exclusive expression patterns of SOX6 and SOX5 in progenitor cells and postmitotic neurons.
Main Results:
- SOX6 and SOX5 exhibit mutually exclusive expression in pallial and subpallial progenitors, respectively, and in their neuronal progeny.
- Loss of SOX6 in pallial progenitors led to the adoption of subpallial developmental programs and mixed dorsal-ventral identity.
- Disruption of SOX6 in postmitotic cortical interneurons impaired their differentiation and subtype diversity.
Conclusions:
- SOX6 is a key regulator of molecular segregation between dorsal and ventral telencephalic progenitors.
- SOX6 plays a critical role in establishing and maintaining the diversity of cortical interneurons during neocortical development.
- These findings highlight SOX6 as a central molecular determinant of progenitor and interneuron heterogeneity in the developing forebrain.
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