Myc activity is required for maintenance of the neuromesodermal progenitor signalling network and for segmentation clock gene oscillations in mouse

Development. 2018 Jul 30;145(14):dev161091. doi: 10.1242/dev.161091.

Abstract

The Myc transcriptional regulators are implicated in a range of cellular functions, including proliferation, cell cycle progression, metabolism and pluripotency maintenance. Here, we investigated the expression, regulation and function of the Myc family during mouse embryonic axis elongation and segmentation. Expression of both cMyc (Myc - Mouse Genome Informatics) and MycN in the domains in which neuromesodermal progenitors (NMPs) and underlying caudal pre-somitic mesoderm (cPSM) cells reside is coincident with WNT and FGF signals, factors known to maintain progenitors in an undifferentiated state. Pharmacological inhibition of Myc activity downregulates expression of WNT/FGF components. In turn, we find that cMyc expression is WNT, FGF and Notch protein regulated, placing it centrally in the signalling circuit that operates in the tail end that both sustains progenitors and drives maturation of the PSM into somites. Interfering with Myc function in the PSM, where it displays oscillatory expression, delays the timing of segmentation clock oscillations and thus of somite formation. In summary, we identify Myc as a component that links NMP maintenance and PSM maturation during the body axis elongation stages of mouse embryogenesis.

Keywords: Embryo; Myc; Neuromesodermal progenitors; Presomitic mesoderm; Segmentation clock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks / genetics*
  • Body Patterning / genetics*
  • CLOCK Proteins / genetics*
  • CLOCK Proteins / metabolism
  • Cell Differentiation
  • Down-Regulation / genetics
  • Embryo, Mammalian / metabolism
  • Female
  • Fibroblast Growth Factor 8 / metabolism
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Mesoderm / cytology*
  • Mesoderm / embryology
  • Mesoderm / metabolism*
  • Mice
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / genetics*
  • Somites / embryology
  • Somites / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Tail / embryology
  • Wnt Proteins / metabolism

Substances

  • Fgf8 protein, mouse
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Wnt Proteins
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • CLOCK Proteins