Grainyhead-like 2 interacts with noggin to regulate tissue fusion in mouse.

Autor:	de Vries ME; Department of Medicine, Monash University Central Clinical School, Prahran, Victoria 3004, Australia.; Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria 3086, Australia., Carpinelli MR; Department of Medicine, Monash University Central Clinical School, Prahran, Victoria 3004, Australia., Fuller JN; Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria 3086, Australia., Sutton Y; Department of Medicine, Monash University Central Clinical School, Prahran, Victoria 3004, Australia., Partridge DD; Department of Medicine, Monash University Central Clinical School, Prahran, Victoria 3004, Australia., Auden A; Department of Medicine, Monash University Central Clinical School, Prahran, Victoria 3004, Australia., Anderson PJ; Australian Craniofacial Unit, Women and Children's Hospital, Adelaide, SA 5005, Australia.; Faculty of Health Sciences, University of Adelaide, Adelaide, SA 5005, Australia.; School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, People's Republic of China., Jane SM; Department of Medicine, Monash University Central Clinical School, Prahran, Victoria 3004, Australia., Dworkin S; Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, Victoria 3086, Australia.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Mar 01; Vol. 151 (5). Date of Electronic Publication: 2024 Feb 28.
DOI:	10.1242/dev.202420
Abstrakt:	Defective tissue fusion during mammalian embryogenesis results in congenital anomalies, such as exencephaly, spina bifida and cleft lip and/or palate. The highly conserved transcription factor grainyhead-like 2 (Grhl2) is a crucial regulator of tissue fusion, with mouse models lacking GRHL2 function presenting with a fully penetrant open cranial neural tube, facial and abdominal clefting (abdominoschisis), and an open posterior neuropore. Here, we show that GRHL2 interacts with the soluble morphogen protein and bone morphogenetic protein (BMP) inhibitor noggin (NOG) to impact tissue fusion during development. The maxillary prominence epithelium in embryos lacking Grhl2 shows substantial morphological abnormalities and significant upregulation of NOG expression, together with aberrantly distributed pSMAD5-positive cells within the neural crest cell-derived maxillary prominence mesenchyme, indicative of disrupted BMP signalling. Reducing this elevated NOG expression (by generating Grhl2-/-;Nog+/- embryos) results in delayed embryonic lethality, partial tissue fusion rescue, and restoration of tissue form within the craniofacial epithelia. These data suggest that aberrant epithelial maintenance, partially regulated by noggin-mediated regulation of BMP-SMAD pathways, may underpin tissue fusion defects in Grhl2-/- mice. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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