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Updated: Nov 18, 2025

Dissection of Xenopus laevis Neural Crest for in vitro Explant Culture or in vivo Transplantation
Published on: March 4, 2014
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.
Abstract:
Protein interaction is critical molecular regulatory activity underlining cellular functions and precise cell fate choices. Using TWIST1 BioID-proximity-labeling and network propagation analyses, we discovered and characterized a TWIST-chromatin regulatory module (TWIST1-CRM) in the neural crest cells (NCC). Combinatorial perturbation of core members of TWIST1-CRM: TWIST1, CHD7, CHD8, and WHSC1 in cell models and mouse embryos revealed that loss of the function of the regulatory module resulted in abnormal differentiation of NCCs and compromised craniofacial tissue patterning. Following NCC delamination, low level of TWIST1-CRM activity is instrumental to stabilize the early NCC signatures and migratory potential by repressing the neural stem cell programs. High level of TWIST1 module activity at later phases commits the cells to the ectomesenchyme. Our study further revealed the functional interdependency of TWIST1 and potential neurocristopathy factors in NCC development.
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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