PRDM paralogs antagonistically balance Wnt/β-catenin activity during craniofacial chondrocyte differentiation.

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 enhanceoso

SUBMITTER: Shull LC 

PROVIDER: S-EPMC8918787 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature