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

Lomeli C. Shull, Ezra S. Lencer, Hyun Min Kim, Susumu Goyama, Mineo Kurokawa, James C. Costello, Kenneth Jones, Kristin B. Artinger

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
JournalDevelopment (Cambridge, England)
Volume149
Issue number4
DOIs
StatePublished - Feb 15 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022. Published by The Company of Biologists Ltd.

Keywords

  • Craniofacial
  • Mecom/Evi1
  • Mouse
  • Neural crest
  • Prdm16
  • Prdm3
  • Wnt/β-catenin
  • Zebrafish

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

Fingerprint

Dive into the research topics of 'PRDM paralogs antagonistically balance Wnt/β-catenin activity during craniofacial chondrocyte differentiation'. Together they form a unique fingerprint.

Cite this