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Sox2-mediated differential activation of Six3.2 contributes to forebrain patterning
Leonardo Beccari1, Ivan Conte, Elsa Cisneros
1Centro de Biología Molecular Severo Ochoa, CSIC-UAM, c/Nicolas Cabrera 1, Madrid 28049, Spain.
Development (Cambridge, England)
|November 19, 2011
Summary
Transcription factors (TFs) like Six3.2 pattern the vertebrate forebrain. Concentration-dependent Six3.2 and Sox2 activities specify brain regions, revealing novel roles in development.
Area of Science:
- Developmental biology
- Neuroscience
- Genetics
Background:
- Vertebrate forebrain patterning involves transcription factors (TFs).
- Widely expressed TFs pose a challenge in understanding regional specification.
- The homeobox TF Six3.2's role in forebrain development is under investigation.
Purpose of the Study:
- To investigate how Six3.2 mediates regional differences in the vertebrate forebrain.
- To elucidate the regulatory mechanisms of Six3.2 and Sox2 in forebrain development.
- To understand the role of TF concentration in patterning the anterior-posterior axis.
Main Methods:
- Genomic analysis in medaka fish.
- Functional assays to determine TF activities.
- Analysis of TF interactions and regulatory networks.
Main Results:
- Six3.2 regulates telencephalic and retinal specification in a concentration-dependent manner, directly controlled by Sox2.
- Six3.2 and Sox2 exhibit antagonistic functions in hypothalamic development.
- Foxg1 and Rx3 are differentially regulated by Six3.2 and Sox2, mediating their activities.
Conclusions:
- Six3.2 diversifies its function in the forebrain through concentration-dependent regulation.
- Sox2 plays a key role in anterior forebrain development.
- Graded TF levels pattern the vertebrate forebrain along the anterior-posterior axis via independent transcriptional networks.
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