Identification and characterization of a novel Schwann and outflow tract endocardial cushion lineage-restricted periostin enhancer

Andrew Lindsley, Paige Snider, Hongming Zhou, Rhonda Rogers, Jian Wang, Michael Olaopa, Agnieszka Kruzynska-Frejtag, Shrinagesh V. Koushik, Brenda Lilly, John B.E. Burch, Anthony B. Firulli, Simon J. Conway

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Periostin is a fasciclin-containing adhesive glycoprotein that facilitates the migration and differentiation of cells that have undergone epithelial-mesenchymal transformation during embryogenesis and in pathological conditions. Despite the importance of post-transformational differentiation as a general developmental mechanism, little is known how periostin's embryonic expression is regulated. To help resolve this deficiency, a 3.9-kb periostin proximal promoter was isolated and shown to drive tissue-specific expression in the neural crest-derived Schwann cell lineage and in a subpopulation of periostin-expressing cells in the cardiac outflow tract endocardial cushions. In order to identify the enhancer and associated DNA binding factor(s) responsible, in vitro promoter dissection was undertaken in a Schwannoma line. Ultimately a 304-bpperi enhancer was identified and shown to be capable of recapitulating 3.9 kbperi-lacZ in vivo spatiotemporal patterns. Further mutational and EMSA analysis helped identify a minimal 37-bp region that is bound by the YY1 transcription factor. The 37-bp enhancer was subsequently shown to be essential for in vivo 3.9 kbperi-lacZ promoter activity. Taken together, these studies identify an evolutionary-conserved YY1-binding 37-bp region within a 304-bp periostin core enhancer that is capable of regulating simultaneous novel tissue-specific periostin expression in the cardiac outflow-tract cushion mesenchyme and Schwann cell lineages.

Original languageEnglish (US)
Pages (from-to)340-355
Number of pages16
JournalDevelopmental Biology
Volume307
Issue number2
DOIs
StatePublished - Jul 15 2007

Keywords

  • Endocardial cushions
  • Heart development
  • lacZ reporter mice
  • Lineage restricted promoter
  • Mouse embryo
  • Periostin
  • Peripheral nervous system
  • Schwann cells

ASJC Scopus subject areas

  • Developmental Biology

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