Evidence from normal expression and targeted misexpression that Bone Morphogenetic Protein-4 (Bmp-4) plays a role in mouse embryonic lung morphogenesis

Saverio Bellusci; Randall Henderson; Glenn Winnier; Tsuyoshi Oikawa; Brigid L. M. Hogan

doi:10.1242/dev.122.6.1693

journal article Jun 01, 1996

Evidence from normal expression and targeted misexpression that Bone Morphogenetic Protein-4 (Bmp-4) plays a role in mouse embryonic lung morphogenesis

Saverio Bellusci Randall Henderson Glenn Winnier Tsuyoshi Oikawa Brigid L. M. Hogan

Development Vol. 122 No. 6 pp. 1693-1702 · The Company of Biologists

View at Publisher Save 10.1242/dev.122.6.1693

Abstract

ABSTRACT
Epithelial-mesenchymal interactions are critical for the branching and differentiation of the lung, but the mechanisms involved are still unclear. To investigate this problem in mouse embryonic lung, we have studied the temporal and spatial expression of genes implicated in the morpho-genesis of other organs. At 11.5 days p.c., hepatocyte nuclear factor-3β (Hnf-3β) is expressed uniformly through-out the epithelium, while Wnt-2 expression is confined to the distal mesenchyme. Sonic hedgehog (Shh) trancripts are found throughout the epithelium, with high levels in the distal tips of the terminal buds, while bone morphogenetic protein-4 (Bmp-4) transcripts are localized at high levels in the distal tips of the epithelium, with lower levels in the adjacent mesenchyme. Epithelial expression is also seen for Bmp-7, but transcripts are less dramatically upregulated at the distal tips. The Type I Bone morphogenetic protein receptor gene(Bmpr/Tfr-11/Brk-1) is expressed at low levels in the epithelium and in the distal mesenchyme. To investigate the role of Bmp-4 in lung development, we have mis-expressed the gene throughout the distal epithelium of transgenic lungs using a surfactant protein C enhancer/promoter. From 15.5 days p.c., transgenic lungs are smaller than normal, with grossly distended terminal buds and, at birth, contain large air-filled sacs which do not support normal lung function. Labeling with BrdU reveals an inhibition of epithelial proliferation in 15.5 days p.c. transgenic lungs. A small but significant stimulation of proliferation of mesenchymal cells is also observed, but this is accompanied by an increase in cell death. In situ hybridization with riboprobes for the proximal airway marker, CC10, and the distal airway marker, SP-C, shows normal differentiation of bronchiolar Clara cells but a reduction in the number of differentiated Type II cells in transgenic lungs. A model is proposed for the role of BMP4 and other signalling molecules in embryonic lung morphogenesis.

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Details

Published: Jun 01, 1996
Vol/Issue: 122(6)
Pages: 1693-1702
License: View

Authors

S

Saverio Bellusci

Vanderbilt University Medical Center 2 Department of Cell Biology , , Nashville, Tennessee 37232-2175 USA

R

Randall Henderson

Vanderbilt University Medical Center 3 Division of Neonatology , , Nashville, Tennessee 37232-2175 USA

G

Glenn Winnier

Vanderbilt University Medical Center 2 Department of Cell Biology , , Nashville, Tennessee 37232-2175 USA

T

Tsuyoshi Oikawa

Vanderbilt University Medical Center 4 Division of Pediatric Nephrology , , Nashville, Tennessee 37232-2175 USA

B

Brigid L. M. Hogan

Vanderbilt University Medical Center 1 Howard Hughes Medical Institute , , Nashville, Tennessee 37232-2175 USA; Vanderbilt University Medical Center 2 Department of Cell Biology , , Nashville, Tennessee 37232-2175 USA

Cite This Article

Saverio Bellusci, Randall Henderson, Glenn Winnier, et al. (1996). Evidence from normal expression and targeted misexpression that Bone Morphogenetic Protein-4 (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development, 122(6), 1693-1702. https://doi.org/10.1242/dev.122.6.1693

Evidence from normal expression and targeted misexpression that Bone Morphogenetic Protein-4 (Bmp-4) plays a role in mouse embryonic lung morphogenesis

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