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Defective Neural Stem and Progenitor Cell Proliferation in Neurodevelopmental Disorders.

Aki Shigenaka1, Eri Nitta1, Tadashi Nakagawa1,2

  • 1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo-Onoda 756-0884, Japan.

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Summary

Defects in neural stem and progenitor cell (NSPC) proliferation disrupt brain development, contributing to neurodevelopmental disorders (NDDs). Understanding these NSPC defects offers potential therapeutic targets for NDDs.

Keywords:
cell cycle regulationchromatin remodelingenvironmental teratogensmicrocephaly and macrocephalyneural stem and progenitor cellsneurodevelopmental disorderssignal transduction

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Neurodevelopmental disorders (NDDs) stem from early brain construction defects.
  • Neural stem and progenitor cells (NSPCs) are crucial for generating diverse neuronal and glial lineages.
  • NSPC proliferation must be tightly regulated by cell cycle and niche cues.

Purpose of the Study:

  • To review mechanisms of defective NSPC proliferation in NDD pathogenesis.
  • To highlight convergence of genetic and environmental factors on NSPC cell cycle control.
  • To identify potential shared therapeutic targets for NDDs.

Main Methods:

  • Review of recent advances in animal models and human pluripotent stem cell-derived brain organoids.
  • Analysis of key signaling pathways (Notch, Wnt, SHH, PI3K-mTOR).
  • Examination of transcriptional and chromatin regulators (PAX6, CHD8, SETD5, ANKRD11).

Main Results:

  • Disrupted NSPC proliferation leads to aberrant brain size and connectivity.
  • Key signaling pathways integrate proliferative cues.
  • Transcriptional regulators govern NSPC cycling.
  • Prenatal exposure to teratogens causes NSPC proliferation defects and microcephaly.

Conclusions:

  • Defective NSPC proliferation is a central mechanism in NDD pathogenesis.
  • Genetic and environmental factors converge on NSPC cell cycle control.
  • Understanding these pathways may reveal shared therapeutic strategies for NDDs.