Profiling NSD3-dependent neural crest gene expression reveals known and novel candidate regulatory factors

Bridget T Jacques-Fricke, Julaine Roffers-Agarwal, Amina O. Hussein, Kendra J. Yoder, Micah D. Gearhart, Laura S. Gammill

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The lysine methyltransferase NSD3 is required for the expression of key neural crest transcription factors and the migration of neural crest cells. Nevertheless, a complete view of the genes dependent upon NSD3 for expression and the developmental processes impacted by NSD3 in the neural crest was lacking. We used RNA sequencing (RNA-seq) to profile transcripts differentially expressed after NSD3 knockdown in chick premigratory neural crest cells, identifying 674 genes. Gene Ontology and gene set enrichment analyses further support a requirement for NSD3 during neural crest development and show that NSD3 knockdown also upregulates ribosome biogenesis. To validate our results, we selected three genes not previously associated with neural crest development, Astrotactin 1 (Astn1), Dispatched 3 (Disp3), and Tropomyosin 1 (Tpm1). Using whole mount in situ hybridization, we show that premigratory neural crest cells express these genes and that NSD3 knockdown downregulates (Astn1 and Disp3) and upregulates (Tpm1) their expression, consistent with RNA-seq results. Altogether, this study identifies novel putative regulators of neural crest development and provides insight into the transcriptional consequences of NSD3 in the neural crest, with implications for cancer.

Original languageEnglish (US)
Pages (from-to)118-130
Number of pages13
JournalDevelopmental Biology
Volume475
DOIs
StatePublished - Jul 1 2021

Bibliographical note

Funding Information:
This work was supported by the National Science Foundation under Grant No. IOS-1354809 (LSG). Additional funding was provided by the University of Minnesota Undergraduate Research Opportunities Program (AOH), the federally funded TRIO Ronald E. McNair Post-Baccalaureate Achievement Program at the University of Minnesota (AOH), the Hamline University Ridgway Forum Fund Partnership award (KJY and BJF), Hamline University Summer Collaborative Undergraduate Research program (KJY and BJF), and Hamline University Biology Lund Fund (KJY).

Publisher Copyright:
© 2021 Elsevier Inc.

Keywords

  • Astrotactin 1
  • Dispatched 3
  • NSD3
  • Neural crest
  • RNA-Sequencing
  • Tropomyosin 1

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