The conserved and divergent roles of Prdm3 and Prdm16 in zebrafish and mouse craniofacial development

Lomeli Carpio Shull, Rwik Sen, Johannes Menzel, Susumu Goyama, Mineo Kurokawa, Kristin Bruk Artinger

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The formation of the craniofacial skeleton is a highly dynamic process that requires proper orchestration of various cellular processes in cranial neural crest cell (cNCC) development, including cell migration, proliferation, differentiation, polarity and cell death. Alterations that occur during cNCC development result in congenital birth defects and craniofacial abnormalities such as cleft lip with or without cleft palate. While the gene regulatory networks facilitating neural crest development have been extensively studied, the epigenetic mechanisms by which these pathways are activated or repressed in a temporal and spatially regulated manner remain largely unknown. Chromatin modifiers can precisely modify gene expression through a variety of mechanisms including histone modifications such as methylation. Here, we investigated the role of two members of the PRDM (Positive regulatory domain) histone methyltransferase family, Prdm3 and Prdm16 in craniofacial development using genetic models in zebrafish and mice. Loss of prdm3 or prdm16 in zebrafish causes craniofacial defects including hypoplasia of the craniofacial cartilage elements, undefined posterior ceratobranchials, and decreased mineralization of the parasphenoid. In mice, while conditional loss of Prdm3 in the early embryo proper causes mid-gestation lethality, loss of Prdm16 caused craniofacial defects including anterior mandibular hypoplasia, clefting in the secondary palate and severe middle ear defects. In zebrafish, prdm3 and prdm16 compensate for each other as well as a third Prdm family member, prdm1a. Combinatorial loss of prdm1a, prdm3, and prdm16 alleles results in severe hypoplasia of the anterior cartilage elements, abnormal formation of the jaw joint, complete loss of the posterior ceratobranchials, and clefting of the ethmoid plate. We further determined that loss of prdm3 and prdm16 reduces methylation of histone 3 lysine 9 (repression) and histone 3 lysine 4 (activation) in zebrafish. In mice, loss of Prdm16 significantly decreased histone 3 lysine 9 methylation in the palatal shelves but surprisingly did not change histone 3 lysine 4 methylation. Taken together, Prdm3 and Prdm16 play an important role in craniofacial development by maintaining temporal and spatial regulation of gene regulatory networks necessary for proper cNCC development and these functions are both conserved and divergent across vertebrates.

Original languageEnglish (US)
Pages (from-to)132-144
Number of pages13
JournalDevelopmental Biology
Volume461
Issue number2
DOIs
StatePublished - May 15 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work is supported by NIH/NIDCR NRSA 1 F32 DE029099-01 postdoctoral fellowship to L.C.S., AHA postdoctoral fellowship to R.S., NIH/NIDCR R01DE024034 to K.B.A. and NIH NINDS P30NS048154 to the CU Anschutz zebrafish core facility.

Funding Information:
This work is supported by NIH/NIDCR NRSA 1 F32 DE029099-01 postdoctoral fellowship to L.C.S., AHA postdoctoral fellowship to R.S., NIH/NIDCR R01DE024034 to K.B.A. and NIH NINDS P30NS048154 to the CU Anschutz zebrafish core facility.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • Craniofacial
  • H3K4me3
  • H3K9me3
  • Neural crest
  • Prdm16
  • Prdm3/Evi1/Mecom

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