TWIST1 and chromatin regulatory proteins interact to guide neural crest cell differentiation

Xiaochen Fan1,2, V Pragathi Masamsetti1, Jane Qj Sun1

  • 1Embryology Unit, Children's Medical Research Institute, The University of Sydney, Sydney, Australia.

Elife
|February 8, 2021
PubMed

Insights

This study identifies a TWIST1-chromatin regulatory module (TWIST1-CRM) crucial for neural crest cell (NCC) development. Its activity levels dictate NCC differentiation and craniofacial patterning, impacting cell fate and migration.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Protein interactions regulate cellular functions and cell fate.
  • Neural crest cells (NCCs) are vital for craniofacial development.
  • TWIST1 is a key transcription factor in developmental processes.

Purpose of the Study:

  • To discover and characterize the TWIST1-chromatin regulatory module (TWIST1-CRM) in NCCs.
  • To elucidate the role of TWIST1-CRM in NCC differentiation and craniofacial patterning.
  • To investigate the functional interplay between TWIST1 and neurocristopathy factors.

Main Methods:

  • TWIST1 BioID-proximity-labeling and network propagation analyses.
  • Combinatorial perturbation of TWIST1-CRM core members (TWIST1, CHD7, CHD8, WHSC1) in cell models and mouse embryos.
  • Analysis of NCC differentiation, migration, and craniofacial tissue patterning.

Main Results:

  • Discovery and characterization of the TWIST1-CRM in NCCs.
  • Loss of TWIST1-CRM function leads to abnormal NCC differentiation and craniofacial defects.
  • Dynamic regulation of TWIST1-CRM activity controls NCC signature stabilization, migration, and ectomesenchyme commitment.
  • Revealed functional interdependency of TWIST1 and neurocristopathy factors in NCC development.

Conclusions:

  • The TWIST1-CRM is essential for proper NCC development and craniofacial patterning.
  • TWIST1-CRM activity levels dynamically regulate NCC fate decisions.
  • Understanding TWIST1-CRM provides insights into neurocristopathies and developmental disorders.

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