TY - JOUR
T1 - Role for ETS domain transcription factors Pea3/Erm in mouse lung development
AU - Liu, Yuru
AU - Jiang, Haiyan
AU - Crawford, Howard C.
AU - Hogan, Brigid L.M.
N1 - Funding Information:
We thank Robert Whitehead for generating the C3 cell line and Jeffery Franklin and members of the Hogan laboratory for helpful comments on the manuscript, and the many people who provided in situ hybridization probes. We thank Kevin Tompkins for generating the transgenic embryos. This work was supported by NIH Grants HD28955 and HL71303.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
AB - 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.
KW - ETS domain proteins
KW - Erm
KW - FGF
KW - Lung
KW - Pea3
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U2 - 10.1016/S0012-1606(03)00359-2
DO - 10.1016/S0012-1606(03)00359-2
M3 - Article
C2 - 12941618
AN - SCOPUS:0042162959
SN - 0012-1606
VL - 261
SP - 10
EP - 24
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -