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Related Experiment Video

Updated: Apr 16, 2026

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
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Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the

Eliska Kuchovska1, Kristina Bartmann1,2, Georgea Raad1

  • 1IUF - Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 14, 2026
PubMed
Summary

This study maps neurodevelopmental disorder pathways to key developmental processes in human cells. It refines the Developmental Neurotoxicity (DNT) in vitro battery (IVB) for better chemical safety assessment.

Keywords:
biological applicability domaindevelopmental neurotoxicityneurosphere assaynew approach methodologysignaling pathways

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Area of Science:

  • Neuroscience
  • Toxicology
  • Developmental Biology

Background:

  • The Developmental Neurotoxicity (DNT) in vitro battery (IVB) is crucial for evaluating chemical safety.
  • Expanding its scope to human diseases requires mapping neurodevelopmental disorder (NDD)-relevant pathways to key neurodevelopmental processes (KNDPs).

Purpose of the Study:

  • To map NDD-related signaling pathways to KNDPs using human neural progenitor cells (NPCs).
  • To assess the impact of pharmacological interventions on these pathways and processes.
  • To refine the biological applicability domain of the DNT IVB.

Main Methods:

  • Utilized primary human fetal neural progenitor cells (NPCs).
  • Applied pharmacological interventions to modulate eighteen NDD pathways.
  • Assessed effects on seven KNDPs: NPC proliferation, radial glia migration, neuronal and oligodendrocyte differentiation and migration, and neurite outgrowth.

Main Results:

  • Sixteen pathways significantly modulated at least one KNDP.
  • Oligodendrocyte differentiation was most sensitive (13 pathways), followed by radial glia migration (11) and NPC proliferation (9).
  • RhoA and mitochondrial complex I pathways showed the broadest effects (5 KNDPs each).

Conclusions:

  • Established functional links between NDD pathways and KNDPs in human cells.
  • Developed an interactive map of human oligodendrocyte development.
  • Enhanced the DNT IVB's mechanistic interpretation and applicability for NDD risk assessment.