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.
Highlights
The protein interactome of TWIST1 was characterized using the biotin identification (BioID) technique which allows for the identification of interactors in their native cellular environment (Figure 1A)
We performed the experiment in cranial neural crest cells (NCC) cell line O9-1 (Ishii et al, 2012) transfected with TWIST1-BirA* (TWIST1 fused to the BirA* biotin ligase)
Given that CHD8 was not previously known to involve in craniofacial development of the mouse embryo, we focused on elucidating the impact of genetic interaction of Chd8 and Twist1 on NCC development in vivo
Summary
The cranial neural crest cell (NCC) lineage originates from the neuroepithelium (Vokes et al, 2007; Groves and LaBonne, 2014; Mandalos and Remboutsika, 2017) and contributes to the craniofacial tissues in vertebrates (Sauka-Spengler and Bronner-Fraser, 2008) including parts of the craniofacial skeleton, connective tissues, melanocytes, neurons, and glia (Kang and Svoboda, 2005; Blentic et al, 2008; Ishii et al, 2012; Theveneau and Mayor, 2012) The development of these tissues is affected in neurocristopathies, which can be traced to mutations in genetic determinants of NCC specification and differentiation (Etchevers et al, 2019). NCCs arise from the neuroepithelium, at the border with the surface ectoderm through the pre-
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