FABP7 controls radial glial scaffold stability during human cortical development.

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Radial glial (RG) cells are vital neural progenitors and structural guides for neuronal migration in the developing cortex.
• Fatty acid-binding protein 7 (FABP7) is a known RG cell marker, but its functional role is unclear.

Purpose of the Study:

• To elucidate the regulatory function of FABP7 in cortical development and its potential link to neurodevelopmental disorders.
• To investigate the molecular mechanisms underlying FABP7's role in maintaining RG cell scaffold integrity.

Main Methods:

• Utilized human fetal brain slices, embryonic mouse models, cerebral organoids, and assembloids for experimental analysis.
• Performed single-cell RNA sequencing to analyze transcriptional changes in FABP7-deficient models.
• Investigated the mevalonate (MVA) pathway and GTPase activity in response to FABP7 loss.

Main Results:

• FABP7 is essential for RG scaffold architecture and proper neuronal positioning.
• FABP7 deficiency causes widespread transcriptional dysregulation, impacting cytoskeleton, cell fate, and stress responses.
• FABP7 knockdown organoids show transcriptomic similarities to autism spectrum disorder (ASD) and recapitulate scaffold defects found in idiopathic autism.

Conclusions:

• FABP7 is a critical regulator of cortical development, maintaining scaffold integrity and neuronal organization.
• Loss of FABP7 disrupts the mevalonate pathway, impairing GTPase function and cytoskeletal organization.
• FABP7's role highlights a link between metabolic signaling, RG cell function, and neurodevelopmental vulnerability in disorders like autism.