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HDAC1 and HDAC2 Regulate Intermediate Progenitor Positioning to Safeguard Neocortical Development
Tianxiang Tang1, Yandong Zhang1, Yafei Wang1
1Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Neuron
|February 3, 2019
Summary
Histone deacetylases HDAC1 and HDAC2 control the position of neural progenitors in the developing brain. Their depletion causes mispositioning, leading to cortical malformations and revealing SVZ microenvironment mechanisms.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Neural progenitors in the developing brain require specific microenvironments for proper function.
- Neocortical intermediate progenitors (IPs) are crucial for brain growth, generating neurons for all cortical layers.
Purpose of the Study:
- To investigate the role of spatial positioning of neural progenitors in neocortical development.
- To elucidate the molecular mechanisms regulating IP positioning within the subventricular zone (SVZ).
Main Methods:
- Studied the function of HDAC1 and HDAC2 in radial glial progenitors during brain development.
- Utilized developmental stage-specific depletion of HDAC1 and HDAC2.
- Identified downstream targets of HDAC1 and HDAC2 involved in IP positioning.
Main Results:
- HDAC1 and HDAC2 are essential for maintaining the spatial organization of IPs in the SVZ.
- Depletion of HDAC1 and HDAC2 leads to IP mispositioning at the ventricular surface.
- Mispositioned IPs result in abnormal neuronal differentiation and cortical malformations.
- Neurogenin2 was identified as a key proneural gene regulated by HDAC1 and HDAC2 for IP positioning.
Conclusions:
- Spatial control of neural progenitor positioning is critical for neocortical development.
- HDAC1 and HDAC2 play a vital role in establishing the SVZ microenvironment by regulating IP positioning.
- Dysregulation of this mechanism can lead to cortical malformations.
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