# Microglial Maturation and Functional Heterogeneity: Mechanistic Links to Neurodevelopmental Disorders

## TL;DR

This review explores how microglia, the brain's immune cells, mature and function during development, and how their malfunction may contribute to neurodevelopmental disorders like epilepsy and autism.

## Contribution

The paper repositions microglia as temporally programmed regulators of brain development and links their dysfunction to neurodevelopmental disorders.

## Key findings

- Microglial maturation is temporally and regionally coordinated with key developmental processes like neurogenesis and myelination.
- Early microglial dysfunction due to genetic or environmental factors can disrupt neural circuit formation and lead to disorders like epilepsy and autism.
- Microglial progenitors follow distinct migratory pathways in mouse and human systems, shaping their functional specialization.

## Abstract

As the brain’s resident macrophages, microglia on the one side are increasingly recognized as essential players in discrete developmental stages, where immune, metabolic, and activity-derived signals are coordinately integrated to guide brain development. On the other side, the precise temporal and molecular coordination of microglial maturation is imperative for the structural and functional integrity of the developing central nervous system (CNS). In this review, we synthesize recent data that reposition microglia from a uniform population of immune sentinels to temporally programmed and regionally specialized regulators of circuit maturation. This involves dissecting the embryonic origins and migratory pathways of microglial progenitors in mouse and human systems and illustrating how gradual transcriptional and morphological maturation aligns the biology of microglia with progressive phases of neurogenesis, synaptic fine-tuning, myelination, and vascular stabilization. In addition, we discuss how individual gene mutations, inflammatory insults during perinatal life, and environmental disturbances intersect with these temporal programs to alter microglial phenotypes and compromise circuit formation. With a special emphasis on epilepsy and autism spectrum disorder, often sharing the common etiology, we illustrate how early malfunction of microglia may drive neural network dysfunction.