Abstract
In Drosophila embryos, the loss of sprouty gene function enhances branching of the respiratory system. Three human sprouty homologues (h-Spry1-3) have been cloned recently, but their function is as yet unknown [1]. Here, we show that a murine sprouty gene (mSpry-2), the product of which shares 97% homology with the respective human protein, is expressed in the embryonic murine lung. We used an antisense oligonucleotide strategy to reduce expression of mSpry-2 by 96%, as measured by competitive reverse transcriptase PCR, in E11. 5 murine embryonic lungs cultured for 4 days [2]. Morphologically, the decrease in mSpry-2 expression resulted in a 72% increase in embryonic murine lung branching morphogenesis as well as a significant increase in expression of the lung epithelial marker genes SP-C, SP-B and SP-A. These results support a striking conservation of function between the Drosophila and mammalian sprouty gene families to negatively modulate respiratory organogenesis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Drosophila / embryology
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Drosophila / growth & development
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Drosophila / physiology*
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Drosophila Proteins*
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Embryonic Induction
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Gene Expression Regulation, Developmental
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Humans
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Insect Proteins / chemistry
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Insect Proteins / genetics
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Insect Proteins / physiology*
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Intracellular Signaling Peptides and Proteins
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Lung / embryology
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Lung / growth & development
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Lung / physiology*
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Male
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Membrane Proteins*
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Mice
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Molecular Sequence Data
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Morphogenesis
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Organ Specificity
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Protein Serine-Threonine Kinases
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Proteins / chemistry
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Proteins / genetics
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Proteins / physiology*
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Respiratory System
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Sequence Alignment
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Sequence Homology, Amino Acid
Substances
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Adaptor Proteins, Signal Transducing
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Drosophila Proteins
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Insect Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Proteins
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SPRY2 protein, human
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sty protein, Drosophila
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Protein Serine-Threonine Kinases
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Spry2 protein, mouse