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FABP7 controls radial glial scaffold stability during human cortical development.

Yuanhao Wang1,2, Xu Zhang1,2, Ru Ba3

  • 1Institute of Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Proceedings of the National Academy of Sciences of the United States of America
|April 15, 2026
PubMed
Summary

Fatty acid-binding protein 7 (FABP7) is crucial for maintaining the radial glial (RG) cell scaffold during brain development. FABP7 deficiency disrupts neuronal positioning and links metabolic pathways to neurodevelopmental disorders like autism.

Keywords:
FABP7autismbrain organoidsmevalonate pathwayradial glial scaffold

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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.