Neuronal Delamination and Outer Radial Glia Generation in Neocortical Development

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Neocortical development relies on neural progenitor cells (apical radial glial cells, aRGs) dividing at the apical surface.
• Neurogenic cell delamination, the detachment of differentiating cells, is essential for their migration and controlled by apical endfeet.
• The apical microenvironment is vital for maintaining neural progenitors, making timely detachment critical for neurogenesis.

Purpose of the Study:

• To elucidate the molecular mechanisms governing neurogenic cell delamination during neocortical development.
• To identify key proteins and pathways regulating the dynamic changes at the apical endfeet during cell detachment.
• To understand the role of specific proteins in controlling progenitor cell division and generating different progenitor types.

Main Methods:

• Analysis of dynamic changes in microtubule-actin-adherens junction (AJ) configurations during cell delamination.
• Investigating transcriptional and posttranscriptional regulation of AJ-related molecules and cytoskeletal architecture.
• Studying the function of interphase centrosome protein AKNA and microtubule-associated protein Lzts1 in cell adhesion and division.

Main Results:

• Cell delamination involves dynamic remodeling of the microtubule-actin-AJ complex at apical endfeet, including AJ constriction and cadherin downregulation.
• Transcriptional suppression of AJ molecules and posttranscriptional regulation of cell adhesion and cytoskeleton are key.
• AKNA destabilizes the microtubule-actin-AJ complex, while Lzts1 inhibits microtubule assembly and activates actomyosin systems, influencing cell division and outer radial glia (oRG) generation.

Conclusions:

• Neurogenic cell delamination is a complex process regulated by coordinated transcriptional and posttranscriptional mechanisms.
• Proteins like AKNA and Lzts1 play critical roles in modulating cell adhesion and cytoskeletal dynamics at the apical endfeet.
• These mechanisms not only control cell delamination but also influence the generation of distinct neural progenitor populations, such as oRGs.