Abstract
The Sonic hedgehog (Shh) cascade is crucial for the patterning of the early lung morphogenesis in mice, but its role in the developing human lung remains to be determined. In the present study, the expression patterns of SHH signaling pathway components, including SHH, PTCH1, SMO, GLI1, GLI2 and GLI3 were examined by in situ hybridization and immunohistochemistry, and compared with the equivalent patterns in mice. Our results showed that, as in mice, SHH was expressed in the epithelium of the developing human lung. However, SHH receptors (PTCH1 and SMO) and SHH signaling effectors (GLI1-3) were strongly detected in the human lung epithelium, but weakly in the mesenchyme, slightly different from their expressions in mice. Furthermore, the expression levels of SHH signaling pathway genes in human lung, but not that of GLI1, were subsequently downregulated at the canalicular stage evaluated by real-time PCR, coincident with a decline in the developing murine lung. In conclusion, in spite of slight differences, the considerable similarities of gene expression in human and mice suggest that conserved molecular networks regulate mammalian lung development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Epithelium / metabolism
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Gene Expression
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Gene Expression Regulation, Developmental*
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Hedgehog Proteins / genetics*
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Hedgehog Proteins / metabolism
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Humans
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Immunohistochemistry
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In Situ Hybridization
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / metabolism
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Lung / embryology*
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Lung / metabolism
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Mesoderm / metabolism
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Mice
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Morphogenesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Patched Receptors
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Patched-1 Receptor
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Polymerase Chain Reaction
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism
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Signal Transduction / genetics*
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Smoothened Receptor
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Zinc Finger Protein GLI1
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Zinc Finger Protein Gli2
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Zinc Finger Protein Gli3
Substances
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DNA-Binding Proteins
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GLI1 protein, human
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GLI2 protein, human
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GLI3 protein, human
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Hedgehog Proteins
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Kruppel-Like Transcription Factors
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Nerve Tissue Proteins
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Nuclear Proteins
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PTCH1 protein, human
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Patched Receptors
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Patched-1 Receptor
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Ptch1 protein, mouse
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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SHH protein, human
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SMO protein, human
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Smoothened Receptor
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Trans-Activators
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Transcription Factors
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Zinc Finger Protein GLI1
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Zinc Finger Protein Gli2
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Zinc Finger Protein Gli3