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Bidirectional interaction between protocadherin 8 and the transcription factor Dbx1 regulates cerebral cortex
Andrzej W Cwetsch1,2,3, Sofia Ferreira1,2, Elodie Delberghe1,2
1Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Team Genetics and Development of the Cerebral Cortex, 75014 Paris, France.
This study reveals a surprising bidirectional relationship between the Dbx1 transcription factor and Pcdh8 cell adhesion molecule during brain development. This interaction unexpectedly influences neuronal identity, cell aggregation, and tissue patterning.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Proper brain development relies on precise tissue patterning and cell-type specification.
- Transcription factors regulate gene expression for neuronal subtype identity.
- Cell adhesion molecules are crucial for cell sorting, migration, and synaptogenesis.
Purpose of the Study:
- To investigate the relationship between transcription factors and cell adhesion molecules in brain development.
- To explore the functional consequences of ectopic Dbx1 expression on cell adhesion and neuronal identity.
- To determine if cell adhesion molecules can reciprocally regulate transcription factor activity and developmental patterning.
Main Methods:
- Ectopic expression of Dbx1 in developing neural tissues.
- Analysis of Pcdh8 expression, cell aggregation, and neuronal identity markers.
- Investigation of Notch signaling pathway involvement in response to Pcdh8 expression.
Main Results:
- Ectopic Dbx1 expression induced spatiotemporally restricted Pcdh8 expression and cell aggregation.
- Ectopic Pcdh8 expression was found to induce Dbx1 expression.
- Pcdh8 influenced apico-basal polarity and dorso-ventral patterning via Notch signaling.
Conclusions:
- Cell adhesion molecules, specifically Pcdh8, are unexpected regulators of cell identity.
- A bidirectional interaction between Dbx1 and Pcdh8 governs neuronal identity and tissue patterning.
- This study redefines the role of cell adhesion molecules in developmental regulation.
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