Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors

Mickael Orgeur, Marvin Martens, Georgeta Leonte, Sonya Nassari, Marie-Ange Bonnin, Stefan T. Boerno, Bernd Timmermann, Jochen Hecht, Delphine Duprez*, Sigmar Stricker*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development.

Original languageEnglish
Article number161208
Pages (from-to)1-17
Number of pages17
JournalDevelopment
Volume145
Issue number7
DOIs
Publication statusPublished - Apr 2018

Keywords

  • Chicken model
  • Limb development
  • Connective tissue differentiation
  • Extracellular matrix
  • Signalling pathways
  • Transcription factors
  • Transcriptional regulatory network
  • TENDON CELL FATE
  • EXTRACELLULAR-MATRIX
  • PRESUMPTIVE LIMB
  • MUSCLE
  • DIFFERENTIATION
  • EXPRESSION
  • BINDING
  • SEQUENCE
  • MORPHOGENESIS
  • PLURIPOTENT

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