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PRDM paralogs antagonistically balance Wnt/β-catenin activity during craniofacial chondrocyte differentiation.
- Source :
-
Development (Cambridge, England) [Development] 2022 Feb 15; Vol. 149 (4). Date of Electronic Publication: 2022 Feb 24. - Publication Year :
- 2022
-
Abstract
- Cranial neural crest cell (NCC)-derived chondrocyte precursors undergo a dynamic differentiation and maturation process to establish a scaffold for subsequent bone formation, alterations in which contribute to congenital birth defects. Here, we demonstrate that transcription factor and histone methyltransferase proteins Prdm3 and Prdm16 control the differentiation switch of cranial NCCs to craniofacial cartilage. Loss of either paralog results in hypoplastic and disorganized chondrocytes due to impaired cellular orientation and polarity. We show that these proteins regulate cartilage differentiation by controlling the timing of Wnt/β-catenin activity in strikingly different ways: Prdm3 represses whereas Prdm16 activates global gene expression, although both act by regulating Wnt enhanceosome activity and chromatin accessibility. Finally, we show that manipulating Wnt/β-catenin signaling pharmacologically or generating prdm3-/-;prdm16-/- double mutants rescues craniofacial cartilage defects. Our findings reveal upstream regulatory roles for Prdm3 and Prdm16 in cranial NCCs to control Wnt/β-catenin transcriptional activity during chondrocyte differentiation to ensure proper development of the craniofacial skeleton.<br />Competing Interests: Competing interests The authors declare no competing or financial interests.<br /> (© 2022. Published by The Company of Biologists Ltd.)
- Subjects :
- Animals
Cartilage cytology
Cartilage metabolism
Chondrocytes cytology
Chondrocytes metabolism
Chondrogenesis
Chromatin metabolism
Chromatin Assembly and Disassembly
DNA-Binding Proteins deficiency
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Gene Expression Regulation, Developmental
MDS1 and EVI1 Complex Locus Protein deficiency
MDS1 and EVI1 Complex Locus Protein genetics
Mice
Mice, Knockout
Neural Crest cytology
Neural Crest metabolism
Regulatory Sequences, Nucleic Acid
Skull cytology
Skull metabolism
Wnt Proteins metabolism
Zebrafish
Zebrafish Proteins deficiency
Zebrafish Proteins genetics
beta Catenin metabolism
Cell Differentiation
MDS1 and EVI1 Complex Locus Protein metabolism
Wnt Signaling Pathway genetics
Zebrafish Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 149
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 35132438
- Full Text :
- https://doi.org/10.1242/dev.200082