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Generating 3D mouse organoids for cortex development and evo-devo.

Hanwen Yu1, Yan Liu2

  • 1Institute for Stem Cell and Neural Regeneration, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

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|December 16, 2025
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Summary

Regulatory differences across mouse subspecies influence brain development. A new organoid model links cis-regulatory variation to neurodevelopmental mechanisms and genetic diseases.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Corticogenesis, the development of the cerebral cortex, involves complex cell-type specification and maturation processes.
  • Understanding how cis-regulatory elements contribute to these processes across different species and evolutionary times is crucial.

Purpose of the Study:

  • To investigate how cis-regulatory differences across mouse subspecies and evolutionary timescales impact cell-type specification and maturation during corticogenesis.
  • To establish a scalable mouse organoid platform for studying neurodevelopmental dynamics.

Main Methods:

  • Development of a scalable mouse organoid platform to recapitulate corticogenesis.
  • Mapping of allele-specific expression within the organoid system.
  • Analysis of cis-regulatory variation and its link to neurodevelopmental mechanisms.

Main Results:

  • The organoid platform successfully recapitulated key developmental dynamics of corticogenesis.
  • Identification of cis-regulatory variations influencing cell-type specification and maturation.
  • Demonstration of a link between cis-regulatory variation and genes associated with neurodevelopmental diseases.

Conclusions:

  • Scalable mouse organoids provide a powerful tool for dissecting cis-regulatory mechanisms in corticogenesis.
  • Cis-regulatory variation plays a significant role in shaping neurodevelopmental trajectories.
  • This research offers insights into the genetic basis of neurodevelopmental disorders.