Modeling Early Neural Crest Development via Induction from hiPSC-Derived Neural Plate Border-like Cells

Nani, Diogo Andrade; Hsia, Gabriella Shih Ping; Passos‐Bueno, Maria Rita; Kobayashi, Gerson Shigeru

doi:10.1007/7651_2021_454

Cited by 1 publication

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“…iNCCs were generated from healthy induced-pluripotent stem cells (iPSC) and characterised as previously described 81 . iPSCs used in this study were NIBSC8, obtained with the National Institute for Biological Standards and Control (UK).…”

Section: Methodsmentioning

confidence: 99%

Neural crest E-cadherin loss drives cleft lip/palate by epigenetic modulation via pro-inflammatory gene–environment interaction

et al. 2023

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Gene–environment interactions are believed to play a role in multifactorial phenotypes, although poorly described mechanistically. Cleft lip/palate (CLP), the most common craniofacial malformation, has been associated with both genetic and environmental factors, with little gene–environment interaction experimentally demonstrated. Here, we study CLP families harbouring CDH1/E-Cadherin variants with incomplete penetrance and we explore the association of pro-inflammatory conditions to CLP. By studying neural crest (NC) from mouse, Xenopus and humans, we show that CLP can be explained by a 2-hit model, where NC migration is impaired by a combination of genetic (CDH1 loss-of-function) and environmental (pro-inflammatory activation) factors, leading to CLP. Finally, using in vivo targeted methylation assays, we demonstrate that CDH1 hypermethylation is the major target of the pro-inflammatory response, and a direct regulator of E-cadherin levels and NC migration. These results unveil a gene–environment interaction during craniofacial development and provide a 2-hit mechanism to explain cleft lip/palate aetiology.

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Section: Methodsmentioning

confidence: 99%