# Architects of the Developing Brain: Cytoskeleton-Organizing Molecules in Neurodevelopmental Disorders

## TL;DR

This review explores how cytoskeleton molecules shape brain development and contribute to neurodevelopmental disorders.

## Contribution

The paper provides a comprehensive overview of cytoskeletal roles in cortical development and their disruption in neurodevelopmental disorders.

## Key findings

- Cytoskeleton components regulate key processes like neuronal migration and synaptogenesis.
- Genetic mutations in cytoskeletal proteins are linked to disorders such as microcephaly and lissencephaly.
- Cytoskeletal dysfunction leads to altered cellular behavior and specific clinical phenotypes.

## Abstract

Different components of the cytoskeleton are very important determinants of brain development. They orchestrate multiple cellular processes involved in all phases of cerebral cortex development. In this review, we summarize current knowledge on the components of the cytoskeleton—microtubules, actin filaments, and intermediate filaments—and their roles in cortical development. We provide a detailed analysis of how cytoskeleton molecules control neuronal progenitor proliferation, neuronal migration, polarization, axon and dendrite specification and outgrowth, and synaptogenesis. We further examine how pathogenic variants in genes encoding cytoskeletal proteins or their regulators disrupt particular steps of neurogenesis and contribute to major neurodevelopmental disorders (NDDs). Focusing on NDDs such as microcephaly, lissencephaly, corpus callosum agenesis, and synaptopathies, we discuss consequences of cytoskeletal dysfunctions causing altered cellular behavior and clinical phenotypes. By linking molecular defects to developmental and phenotypic consequences, this review highlights the cytoskeleton as a central element in neurodevelopmental pathologies and underscores its potential as a target for future therapeutic strategies.