Related Experiment Video

Updated: Feb 14, 2026

Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay
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Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay

Published on: September 27, 2024

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Microglial Maturation and Functional Heterogeneity: Mechanistic Links to Neurodevelopmental Disorders

Pariya Khodabakhsh1, Olga Garaschuk1

  • 1Institute of Physiology, Department of Neurophysiology, Eberhard Karls University of Tübingen, 72074 Tübingen, Germany.

International Journal of Molecular Sciences
|February 13, 2026
PubMed

Insights

Microglia, the brain's immune cells, are crucial for development. This review highlights their specialized roles in brain maturation and how their early dysfunction can lead to neurological disorders like epilepsy and autism spectrum disorder.

Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Microglia, the central nervous system (CNS) resident macrophages, are increasingly recognized for their critical roles in brain development.
  • Their precise temporal and molecular maturation is essential for the structural and functional integrity of the developing CNS.

Purpose of the Study:

  • To synthesize recent findings that reframe microglia from uniform immune cells to temporally programmed, regionally specialized regulators of circuit maturation.
  • To dissect the embryonic origins and migratory pathways of microglial progenitors.
  • To illustrate how microglial maturation aligns with key neurodevelopmental processes.

Main Methods:

  • Review of recent scientific literature and data synthesis.
  • Dissection of embryonic origins and migratory pathways of microglial progenitors in mouse and human systems.
  • Analysis of transcriptional and morphological maturation of microglia.

Main Results:

  • Microglia are repositioned from a uniform population to temporally programmed and regionally specialized regulators of circuit maturation.
  • Microglial maturation aligns with neurogenesis, synaptic refinement, myelination, and vascular stabilization.
  • Gene mutations, perinatal inflammation, and environmental factors can disrupt microglial programming, impairing circuit formation.

Conclusions:

  • Early microglial malfunction can drive neural network dysfunction, contributing to conditions like epilepsy and autism spectrum disorder.
  • Understanding the temporal and regional specialization of microglia is key to addressing developmental neurological disorders.
Keywords:
autism spectrum disorderscircuit maturationepileptogenesismicroglianeurodevelopmentsynaptic pruning

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