Role for ETS domain transcription factors Pea3/Erm in mouse lung development

Yuru Liu, Haiyan Jiang, Howard C. Crawford, Brigid L M Hogan

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

During the development of the mouse lung, the expression of a number of genes, including those encoding growth factors and components of their downstream signaling pathways, is enriched in the epithelium and/or mesenchyme of the distal buds. In this location, they regulate processes such as cell proliferation, branching morphogenesis, and the differentiation of specialized cell types. Here, we report that the expression of Pea3 and Erm (or Etv5, Ets variant gene 5), which encode Pea3 subfamily ETS domain transcription factors, is initially restricted to the distal buds of the developing mouse lung. Erm is transcribed exclusively in the epithelium, while Pea3 is expressed in both epithelium and mesenchyme. Erm/Pea3 are downstream of FGF signaling from the mesenchyme, but their responses toward different FGFs are not the same. The functions of the two proteins were investigated by transgenic expression of a repressor form of Erm specifically in the embryonic lung epithelium. When examined at E18.5, the distal epithelium of transgenic lungs is composed predominantly of immature type II cells, while no mature type I cells are observed. In contrast, the differentiation of proximal epithelial cells, including ciliated cells and Clara cells, appears to be unaffected. A model is proposed for the role of Pea3/Erm during the dynamic process of lung bud outgrowth and proximal-distal differentiation, in response to FGF signaling. Our results provide the first functional evidence that Pea3 subfamily members play a role in epithelial-mesenchymal interactions during lung organogenesis.

Original languageEnglish (US)
Pages (from-to)10-24
Number of pages15
JournalDevelopmental Biology
Volume261
Issue number1
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

Transcription Factors
Epithelium
Lung
Mesoderm
Organogenesis
Morphogenesis
Genes
ETS Motif
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Cell Proliferation
Proteins

Keywords

  • Erm
  • ETS domain proteins
  • FGF
  • Lung
  • Pea3

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Role for ETS domain transcription factors Pea3/Erm in mouse lung development. / Liu, Yuru; Jiang, Haiyan; Crawford, Howard C.; Hogan, Brigid L M.

In: Developmental Biology, Vol. 261, No. 1, 01.09.2003, p. 10-24.

Research output: Contribution to journalArticle

Liu, Yuru ; Jiang, Haiyan ; Crawford, Howard C. ; Hogan, Brigid L M. / Role for ETS domain transcription factors Pea3/Erm in mouse lung development. In: Developmental Biology. 2003 ; Vol. 261, No. 1. pp. 10-24.
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