Identification of oscillatory genes in somitogenesis from functional genomic analysis of a human mesenchymal stem cell model

Dilusha A. William, Biagio Saitta, Joshua D. Gibson, Jeremy Traas, Vladimir Markov, Dorian M. Gonzalez, William Sewell, Douglas M. Anderson, Stephen Pratt, Eric F. Rappaport, Kenro Kusumi

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

During somitogenesis, oscillatory expression of genes in the notch and wnt signaling pathways plays a key role in regulating segmentation. These oscillations in expression levels are elements of a species-specific developmental mechanism. To date, the periodicity and components of the human clock remain unstudied. Here we show that a human mesenchymal stem/stromal cell (MSC) model can be induced to display oscillatory gene expression. We observed that the known cycling gene HES1 oscillated with a 5 h period consistent with available data on the rate of somitogenesis in humans. We also observed cycling of Hes1 expression in mouse C2C12 myoblasts with a period of 2 h, consistent with previous in vitro and embryonic studies. Furthermore, we used microarray and quantitative PCR (Q-PCR) analysis to identify additional genes that display oscillatory expression both in vitro and in mouse embryos. We confirmed oscillatory expression of the notch pathway gene Maml3 and the wnt pathway gene Nkd2 by whole mount in situ hybridization analysis and Q-PCR. Expression patterns of these genes were disrupted in Wnt3atm1Amc mutants but not in Dll3pu mutants. Our results demonstrate that human and mouse in vitro models can recapitulate oscillatory expression observed in embryo and that a number of genes in multiple developmental pathways display dynamic expression in vitro.

Original languageEnglish (US)
Pages (from-to)172-186
Number of pages15
JournalDevelopmental Biology
Volume305
Issue number1
DOIs
StatePublished - May 1 2007

Keywords

  • Cycling
  • Fourier
  • Mesenchymal
  • Microarray
  • Notch pathway
  • Oscillatory
  • Segmentation
  • Somite
  • Somitogenesis
  • Stem cell
  • Wnt pathway

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    William, D. A., Saitta, B., Gibson, J. D., Traas, J., Markov, V., Gonzalez, D. M., Sewell, W., Anderson, D. M., Pratt, S., Rappaport, E. F., & Kusumi, K. (2007). Identification of oscillatory genes in somitogenesis from functional genomic analysis of a human mesenchymal stem cell model. Developmental Biology, 305(1), 172-186. https://doi.org/10.1016/j.ydbio.2007.02.007