PMID- 9006067
OWN - NLM
STAT- MEDLINE
DCOM- 19970224
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 124
IP  - 1
DP  - 1997 Jan
TI  - Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and 
      morphogenesis.
PG  - 53-63
AB  - Branching morphogenesis of the embryonic lung requires interactions between the 
      epithelium and the mesenchyme. Previously, we reported that Sonic hedgehog (Shh) 
      transcripts are present in the epithelium of the developing mouse lung, with 
      highest levels in the terminal buds. Here, we report that transcripts of mouse 
      patched (Ptc), the homologue of a Drosophila gene encoding a putative 
      transmembrane protein required for hedgehog signaling, are expressed at high 
      levels in the mesenchyme adjacent to the end buds. To investigate the function of 
      SHH in lung development, Shh was overexpressed throughout the distal epithelium, 
      using the surfactant protein-C (SP-C)-enhancer/promoter. Beginning around 16.5 
      dpc, when Shh and Ptc RNA levels are normally both declining, this treatment 
      caused an increase in the ratio of interstitial mesenchyme to epithelial tubules 
      in transgenic compared to normal lungs. Transgenic newborn mice die soon after 
      birth. Histological analysis of the lungs at the light and electron microscope 
      level shows an abundance of mesenchyme and the absence of typical alveoli. In 
      vivo BrdU labeling indicates that Shh overexpression results in increased 
      mesenchymal and epithelial cell proliferation at 16.5 and 17.5 dpc. However, 
      analysis of CC-10 and SP-C expression reveals no significant inhibition in the 
      differentiation of proximal and distal epithelial cells. The expression of genes 
      potentially regulated by SHH was also examined. No difference could be observed 
      between transgenic and control lungs in either the level or distribution of Bmp4, 
      Wnt2 and Fgf7 RNA. By contrast, Ptc is clearly upregulated in the transgenic 
      lung. These results thus establish a role for SHH in lung morphogenesis, and 
      suggest that SHH normally regulates lung mesenchymal cell proliferation in vivo.
FAU - Bellusci, S
AU  - Bellusci S
AD  - Department of Cell Biology, Vanderbilt University Medical Center, Nashville, 
      Tennessee 37232-2175, USA.
FAU - Furuta, Y
AU  - Furuta Y
FAU - Rush, M G
AU  - Rush MG
FAU - Henderson, R
AU  - Henderson R
FAU - Winnier, G
AU  - Winnier G
FAU - Hogan, B L
AU  - Hogan BL
LA  - eng
GR  - HD28955/HD/NICHD NIH HHS/United States
GR  - HL14214/HL/NHLBI NIH HHS/United States
GR  - ST32HL07256/ST/OHS HRSA HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (DNA Primers)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proteolipids)
RN  - 0 (Pulmonary Surfactants)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Animals
MH  - DNA Primers
MH  - Drosophila
MH  - Embryonic Induction
MH  - Embryonic and Fetal Development
MH  - Enhancer Elements, Genetic
MH  - Epithelial Cells
MH  - Epithelium/physiology
MH  - Female
MH  - Hedgehog Proteins
MH  - In Situ Hybridization
MH  - Liver/embryology/metabolism
MH  - Lung/cytology/*embryology/ultrastructure
MH  - Mesoderm/cytology/physiology
MH  - Mice
MH  - Mice, Transgenic
MH  - Morphogenesis
MH  - Polymerase Chain Reaction
MH  - Pregnancy
MH  - Promoter Regions, Genetic
MH  - *Protein Biosynthesis
MH  - Proteins/genetics
MH  - Proteolipids/biosynthesis
MH  - Pulmonary Surfactants/biosynthesis
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - *Trans-Activators
MH  - Transcription, Genetic
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1242/dev.124.1.53 [doi]
PST - ppublish
SO  - Development. 1997 Jan;124(1):53-63. doi: 10.1242/dev.124.1.53.