Tissue interactions pattern the mesenchyme of the embryonic mouse lung.
The mechanisms that control proliferation and differentiation of embryonic lung mesenchyme are largely unknown. We describe an explant system in which exogenous recombinant N-Sonic Hedgehog (N-Shh) protein sustains the survival and proliferation of lung mesenchyme in a dose-dependent manner. In addition, Shh upregulates several mesenchymal cell markers, including its target gene Patched (Ptc), intercellular signaling genes Bone Morphogenetic Protein-4 (Bmp4) and Noggin (Nog), and smooth muscle actin and myosin. In explants exposed to N-Shh in the medium, these products are upregulated throughout the mesenchyme, but not in the periphery. This exclusion zone correlates with the presence of an overlying mesothelial layer, which, as in vivo, expresses Fibroblast Growth Factor 9 (Fgf9). Recombinant Fgf9 protein inhibits the differentiation response of the mesenchyme to N-Shh, but does not affect proliferation. We propose a model for how factors made by two epithelial cell populations, the inner endoderm and the outer jacket of mesothelium, coordinately regulate the proliferation and differentiation of the lung mesoderm.
Weaver
Molly
M
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232-2175, USA.
Batts
Lorene
L
Hogan
Brigid L M
BL
D000199:Actins / Q000235:genetics / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D019521:Body Patterning; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000196:embryology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008954:Models, Biological; D009218:Myosins / Q000235:genetics / Q000502:physiology; D009924:Organ Culture Techniques; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000494:pharmacology / Q000502:physiology; D000099176:Noggin Protein
D000199:Actins; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009218:Myosins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011506:Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D015534:Trans-Activators; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C496460:Fgf9 protein, mouse; C000606240:Ptch1 protein, mouse