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Prdm8 regulates the morphological transition at multipolar phase during neocortical development.
Mayuko Inoue1, Takao Kuroda2, Aya Honda2
1Laboratory of Neural Differentiation, Graduate School of Brain Science, Doshisha University, Kyoto, Japan ; Department of Molecular and Cellular Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Plos One
|February 4, 2014
Summary
The PR domain protein Prdm8 regulates the duration of the multipolar neuron stage in brain development by controlling cell morphology transitions. Its expression impacts neuron positioning and differentiation during neocortical development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Neocortical development involves precise cell migration and differentiation.
- The multipolar phase is a critical stage in neuronal development, preceding terminal differentiation.
- Understanding the regulators of multipolar phase duration is key to understanding brain formation.
Purpose of the Study:
- To investigate the role of the PR domain protein Prdm8 in regulating the multipolar phase of neuronal development.
- To determine how Prdm8 controls the timing of morphological transitions during neocortical development.
- To identify genes and pathways influenced by Prdm8 during late and terminal multipolar phases.
Main Methods:
- Utilized a Prdm8-mVenus reporter mouse line to track Prdm8 expression patterns.
- Performed in utero electroporation for gain- and loss-of-function analysis of Prdm8 in the neocortex.
- Conducted postnatal analysis to assess neuronal positioning and differentiation.
- Analyzed gene expression, focusing on guidance molecules during multipolar phases.
Main Results:
- Prdm8 is predominantly expressed in the intermediate zone during late and terminal multipolar phases, correlating with Unc5D expression.
- Prdm8 knockdown led to premature transition to bipolar morphology and altered neuron positioning, with some cells failing to acquire correct laminar features.
- Prdm8 overexpression maintained multipolar morphology.
- Prdm8 regulates the expression of guidance molecules involved in neuronal development.
Conclusions:
- Prdm8 is a critical regulator controlling the length of the multipolar phase by timing morphological transitions.
- Prdm8-mediated regulation of cell morphology and guidance molecule expression is essential for proper neocortical development and neuronal lamination.
- Dysregulation of Prdm8 impacts neuronal positioning and differentiation, highlighting its importance in brain formation.
