Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development

Molly Weaver; Jonathan M. Yingling; N. Ray Dunn; Saverio Bellusci; Brigid L. M. Hogan

doi:10.1242/dev.126.18.4005

journal article Sep 15, 1999

Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development

Molly Weaver Jonathan M. Yingling N. Ray Dunn Saverio Bellusci Brigid L. M. Hogan

Development Vol. 126 No. 18 pp. 4005-4015 · The Company of Biologists

View at Publisher Save 10.1242/dev.126.18.4005

Abstract

ABSTRACT
In the mature mouse lung, the proximal-distal (P-D) axis is delineated by two distinct epithelial subpopulations: the proximal bronchiolar epithelium and the distal respiratory epithelium. Little is known about the signaling molecules that pattern the lung along the P-D axis. One candidate is Bone Morphogenetic Protein 4 (Bmp4), which is expressed in a dynamic pattern in the epithelial cells in the tips of growing lung buds. Previous studies in which Bmp4 was overexpressed in the lung endoderm (Bellusci, S., Henderson, R., Winnier, G., Oikawa, T. and Hogan, B. L. M. (1996) Development 122, 1693-1702) suggested that this factor plays an important role in lung morphogenesis. To further investigate this question, two complementary approaches were utilized to inhibit Bmp signaling in vivo. The Bmp antagonist Xnoggin and, independently, a dominant negative Bmp receptor (dnAlk6), were overexpressed using the surfactant protein C (Sp-C) promoter/enhancer. Inhibiting Bmp signaling results in a severe reduction in distal epithelial cell types and a concurrent increase in proximal cell types, as indicated by morphology and expression of marker genes, including the proximally expressed hepatocyte nuclear factor/forkhead homologue 4 (Hfh4) and Clara cell marker CC10, and the distal marker Sp-C. In addition, electron microscopy demonstrates the presence of ciliated cells, a proximal cell type, in the most peripheral regions of the transgenic lungs. We propose a model in which Bmp4 is a component of an apical signaling center controlling P-D patterning. Endodermal cells at the periphery of the lung, which are exposed to high levels of Bmp4, maintain or adopt a distal character, while cells receiving little or no Bmp4 signal initiate a proximal differentiation program.

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Details

Published: Sep 15, 1999
Vol/Issue: 126(18)
Pages: 4005-4015
License: View

Authors

M

Molly Weaver

Vanderbilt University Medical Center 2 Department of Cell Biology , , Nashville, TN, USA

J

Jonathan M. Yingling

Howard Hughes Medical Institute and Vanderbilt University Medical Center 1 , Nashville, TN, USA; Vanderbilt University Medical Center 2 Department of Cell Biology , , Nashville, TN, USA

N

N. Ray Dunn

Vanderbilt University Medical Center 2 Department of Cell Biology , , Nashville, TN, USA

Howard Hughes Medical Institute and Vanderbilt University Medical Center 1 , Nashville, TN, USA; Vanderbilt University Medical Center 2 Department of Cell Biology , , Nashville, TN, USA

Cite This Article

Molly Weaver, Jonathan M. Yingling, N. Ray Dunn, et al. (1999). Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development. Development, 126(18), 4005-4015. https://doi.org/10.1242/dev.126.18.4005

Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development

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