TWIST1 and chromatin regulatory proteins interact to guide neural crest cell differentiation
- CMRI, The University of Sydney, Australia
Abstract
Protein interaction is critical molecular regulatory activity underlining cellular functions and precise cell fate choices. Using TWIST1 BioID-proximity-labelling 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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Sequencing data have been deposited in GEO under accession codes GSE130251. External data analyzed has been listed in Supplementary File 6.
-
TWIST1 direct targets during embryonic stem cell differentiation [ChIP-seq]NCBI Gene Expression Omnibus, GSE130251.
-
Dissecting neural differentiation regulatory networks through epigenetic footprintingNCBI Gene Expression Omnibus, GSE62193.
-
AF22_H3K36me3NCBI Gene Expression Omnibus, GSM2902410.
-
Genome-wide maps of chromatin state during the differentiation of hESC into hNECs (ChIP-Seq)NCBI Gene Expression Omnibus, GSM1973975.
-
Transcription factors interfering with dedifferentiation induce direct conversionNCBI Gene Expression Omnibus, GSM1012189.
-
Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cellsNCBI Gene Expression Omnibus, GSM1711445.
-
Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional ProgramsThe European Nucleotide Archive, ERS580651.
-
Spatio-temporal structure of cell fate decisions in murine neural crestNCBI Gene Expression Omnibus, GSE129114.
Article and author information
Author details
Funding
National Health and Medical Research Council (1066832,1079160,1003100,1110751)
- Mark E Graham
- Patrick PL Tam
Australian Research Council (1094008)
- Xiaochen Fan
- Patrick PL Tam
University of Sydney
- Xiaochen Fan
Children's Medical Research Institute
- Xiaochen Fan
- Pierre Osteil
- Nicolas Fossat
Carlsbergfondet (CF15-1056,CF16-0066)
- Kasper Engholm-Keller
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experimentations were performed in compliance with animal ethics and welfare guidelines stipulated by the Children's Medical Research Institute/Children's Hospital at Westmead Animal Ethics Committee, protocol number C230.
Copyright
© 2021, Fan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,031
- views
-
- 493
- downloads
-
- 33
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
TWIST1 and chromatin regulatory proteins interact to guide neural crest cell differentiation
eLife 10:e62873.
https://doi.org/10.7554/eLife.62873
Further reading
-
- Cell Biology
Cell migration towards stiff substrates has been coined as durotaxis and implicated in development, wound healing, and cancer, where complex interplays between immune and non-immune cells are present. Compared to the emerging mechanisms underlying the strongly adhesive mesenchymal durotaxis, little is known about whether immune cells - migrating in amoeboid mode - could follow mechanical cues. Here, we develop an imaging-based confined migration device with a stiffness gradient. By tracking live cell trajectory and analyzing the directionality of T cells and neutrophils, we observe that amoeboid cells can durotax. We further delineate the underlying mechanism to involve non-muscle myosin IIA (NMIIA) polarization towards the soft-matrix-side but may not require differential actin flow up- or down-stiffness gradient. Using the protista Dictyostelium, we demonstrate the evolutionary conservation of amoeboid durotaxis. Finally, these experimental phenomena are theoretically captured by an active gel model capable of mechanosensing. Collectively, these results may shed new lights on immune surveillance and recently identified confined migration of cancer cells, within the mechanically inhomogeneous tumor microenvironment or the inflamed fibrotic tissues.
-
- Cell Biology
- Developmental Biology
How cells regulate the size of their organelles remains a fundamental question in cell biology. Cilia, with their simple structure and surface localization, provide an ideal model for investigating organelle size control. However, most studies on cilia length regulation are primarily performed on several single-celled organisms. In contrast, the mechanism of length regulation in cilia across diverse cell types within multicellular organisms remains a mystery. Similar to humans, zebrafish contain diverse types of cilia with variable lengths. Taking advantage of the transparency of zebrafish embryos, we conducted a comprehensive investigation into intraflagellar transport (IFT), an essential process for ciliogenesis. By generating a transgenic line carrying Ift88-GFP transgene, we observed IFT in multiple types of cilia with varying lengths. Remarkably, cilia exhibited variable IFT speeds in different cell types, with longer cilia exhibiting faster IFT speeds. This increased IFT speed in longer cilia is likely not due to changes in common factors that regulate IFT, such as motor selection, BBSome proteins, or tubulin modification. Interestingly, longer cilia in the ear cristae tend to form larger IFT compared to shorter spinal cord cilia. Reducing the size of IFT particles by knocking down Ift88 slowed IFT speed and resulted in the formation of shorter cilia. Our study proposes an intriguing model of cilia length regulation via controlling IFT speed through the modulation of the size of the IFT complex. This discovery may provide further insights into our understanding of how organelle size is regulated in higher vertebrates.
