Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation

Yu Takahashi, Atsuya Takagi, Shuichi Hiraoka, Haruhiko Koseki, Jun Kanno, Alan Rawls, Yumiko Saga

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Mesp2 and Paraxis are basic helix-loop-helix (bHLH) -type transcription factors coexpressed in the presomitic mesoderm (PSM) and are required for normal somite formation. Here, we show that Mesp2/Paraxis double-null mice exhibit a distinct phenotype unexpected from either Mesp2 or Paraxis single-null mice. In the posterior region of the body, most of the skeletal components of both the vertebral body and neural arches are severely reduced and only a rudimental lamina and ribs remain, indicating a strong genetic interaction in the sclerotomal cell lineage. However, yeast two-hybrid analyses revealed no direct interaction between Mesp2 and Paraxis. The Mesp2/Paraxis double-null embryo has caudalized somites, revealed by expanded Uncx4.1 expression pattern observed in the Mesp2-null embryo, but the expression level of Uncx4.1 was significantly decreased in mature somites, indicative of hypoplasia of lateral sclerotome derivatives. By focusing on vertebral column formation, we found that expressions of Pax1, Nkx3.1, and Bapx1 are regulated by Paraxis and that Pax9 expression was severely affected in the Mesp2/Paraxis double-null embryo. Furthermore, the expression of Pax3, a crucial factor for hypaxial muscle differentiation, is regulated by both Mesp2 and Paraxis in the anteriormost PSM and nascent somite region. The present data strongly suggest that patterning events by bHLH-type transcription factors have deep impacts on regional chondrogenic and myogenic differentiation of somitic cells, mainly by means of control of Pax genes.

Original languageEnglish (US)
Pages (from-to)1484-1494
Number of pages11
JournalDevelopmental Dynamics
Volume236
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Somites
Transcription Factors
Basic Helix-Loop-Helix Transcription Factors
Embryonic Structures
Mesoderm
Body Regions
Ribs
Cell Lineage
Cell Differentiation
Spine
Yeasts
Phenotype
Muscles
Genes

Keywords

  • bHLH factor
  • Pax genes
  • Sclerotome
  • Somitogenesis
  • Vertebra

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation. / Takahashi, Yu; Takagi, Atsuya; Hiraoka, Shuichi; Koseki, Haruhiko; Kanno, Jun; Rawls, Alan; Saga, Yumiko.

In: Developmental Dynamics, Vol. 236, No. 6, 06.2007, p. 1484-1494.

Research output: Contribution to journalArticle

Takahashi, Y, Takagi, A, Hiraoka, S, Koseki, H, Kanno, J, Rawls, A & Saga, Y 2007, 'Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation', Developmental Dynamics, vol. 236, no. 6, pp. 1484-1494. https://doi.org/10.1002/dvdy.21178
Takahashi, Yu ; Takagi, Atsuya ; Hiraoka, Shuichi ; Koseki, Haruhiko ; Kanno, Jun ; Rawls, Alan ; Saga, Yumiko. / Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation. In: Developmental Dynamics. 2007 ; Vol. 236, No. 6. pp. 1484-1494.
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