Loss of Wiz Function Affects Methylation Pattern in Palate Development and Leads to Cleft Palate

0544116 - ÚMG 2022 RIV CH eng J - Článek v odborném periodiku
Buková, Ivana - Szczerkowska, Katarzyna - Procházková, Michaela - Beck, Inken - Procházka, Jan - Sedláček, Radislav
Loss of Wiz Function Affects Methylation Pattern in Palate Development and Leads to Cleft Palate.
Frontiers in Cell and Developmental Biology. Roč. 9, June (2021), č. článku 620692. ISSN 2296-634X. E-ISSN 2296-634X
Grant CEP: GA MŠMT(CZ) LQ1604; GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2018126; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT ED2.1.00/19.0395; GA MŠMT EF16_013/0001789; GA ČR GA19-21696S
Institucionální podpora: RVO:68378050
Klíčová slova: Wiz * G9a * glp * histone methylation * cleft palate * development * craniofacial
Obor OECD: Developmental biology
Impakt faktor: 6.081, rok: 2021
Způsob publikování: Open access
https://www.frontiersin.org/articles/10.3389/fcell.2021.620692/full

WIZ (Widely Interspaced Zinc Finger) is associated with the G9a-GLP protein complex, a key H3K9 methyltransferase suggesting a role in transcriptional repression. However, its role in embryonic development is poorly described. In order to assess the loss of function of WIZ, we generated CRISPR/Cas9 WIZ knockout mouse model with 32 nucleotide deletion. Observing the lethality status, we identified the WIZ knockouts to be subviable during embryonic development and non-viable after birth. Morphology of developing embryo was analyzed at E14.5 and E18.5 and our findings were supported by microCT scans. Wiz KO showed improper development in multiple aspects, specifically in the craniofacial area. In particular, shorter snout, cleft palate, and cleft eyelids were present in mutant embryos. Palatal shelves were hypomorphic and though elevated to a horizontal position on top of the tongue, they failed to make contact and fuse. By comparison of proliferation pattern and histone methylation in developing palatal shelves we brought new evidence of importance WIZ dependent G9a-GLP methylation complex in craniofacial development, especially in palate shelf fusion.
Trvalý link: http://hdl.handle.net/11104/0321166