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Updated: Jun 24, 2025
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Transplantation of Chemogenetically Engineered Cortical Interneuron Progenitors into Early Postnatal Mouse Brains
Published on: August 26, 2019
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Defining cis-regulatory elements and transcription factors that control human cortical interneuron development
Gareth Chapman1, Julianna Determan1, Haley Jetter1
1Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Iscience
|June 3, 2024
Summary
Disruptions in human cortical interneuron (cIN) development are linked to neurodevelopmental disorders. This study identified key regulatory elements and transcription factors, including RFX3 and RFX4, crucial for cIN development and progenitor specification.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Human cortical interneurons (cINs) are vital for brain function, yet their developmental disruptions contribute to neurodevelopmental disorders.
- Understanding the regulatory mechanisms governing human cIN development is critical for addressing these disorders.
Purpose of the Study:
- To create an atlas of cis-regulatory elements (CREs) controlling human cIN development.
- To identify transcription factors (TFs) involved in human interneuron progenitor specification.
- To investigate the roles of RFX3 and RFX4 in human cIN development.
Main Methods:
- Derivation of human cINs from human embryonic stem cells.
- Chromatin state profiling to map CREs.
- Identification of candidate TFs binding to CREs.
- RFX3 and RFX4 knockdown models to assess gene function.
Main Results:
- An atlas of CREs regulating human cIN development was generated.
- RFX3 and RFX4 were identified as candidate TFs involved in interneuron progenitor specification.
- RFX3 deficiency led to precocious neuronal differentiation.
- RFX4 deficiency resulted in the cessation of progenitor cell proliferation.
Conclusions:
- This study defined key cis-regulatory elements controlling human interneuron development.
- New roles for RFX3 and RFX4 in human interneuron progenitor specification were uncovered.
- These findings provide insights into the genetic underpinnings of neurodevelopmental disorders.
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