Extracellular LGALS3BP regulates neural progenitor position and relates to human cortical complexity

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Basal progenitors (BPs) are vital for neuronal expansion in gyrencephalic brains like humans.
• Understanding gene expression in human BP delamination and function is limited.
• LGALS3BP, a known cancer biomarker, is enriched in human neural progenitors (NPCs).

Purpose of the Study:

• To investigate the role of LGALS3BP in human brain development.
• To elucidate the mechanisms underlying LGALS3BP's function in neural progenitor cells.
• To explore the link between LGALS3BP variants and cortical development alterations.

Main Methods:

• Analysis of individuals with LGALS3BP de novo variants.
• Utilizing cerebral organoids, human fetal tissues, and mouse models.
• Employing single-cell RNA-sequencing and proteomics.

Main Results:

• LGALS3BP de novo variants correlate with altered cortical gyrification, sulcal depth, surface area, and thickness.
• LGALS3BP regulates NPC positioning in the developing brain.
• LGALS3BP influences NPC migration via extracellular matrix interactions.

Conclusions:

• LGALS3BP plays a significant role in regulating neural progenitor cell behavior.
• Temporal LGALS3BP expression is proposed to extrinsically influence corticogenesis and gyrification.
• LGALS3BP represents a novel target for understanding human brain development and associated disorders.