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

Ioanna Mastromina, Laure Verrier, Joana Clara Silva, Kate Storey, Jacqueline Dale (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
135 Downloads (Pure)

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 NMPmaintenance and PSMmaturation during the body axis elongation stages of mouse embryogenesis.

Original languageEnglish
Article numberdev161091
Pages (from-to)1-14
Number of pages14
JournalDevelopment
Volume145
Issue number14
DOIs
Publication statusPublished - 30 Jul 2018

Keywords

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

Fingerprint

Dive into the research topics of 'Myc activity is required for maintenance of the neuromesodermal progenitor signalling network and for segmentation clock gene oscillations in mouse'. Together they form a unique fingerprint.

Cite this