The Specific Aims are: 1)To determine the temporo-spatial localization of expression of mspry2 and to compare it with the respective temporo-spatial distribution of mspry1, 3, and 4 as well as with that of key FGF ligands (7 and 10), key FGF receptors (FGF-R2), and key effectors (phosphorylated MAPK) in early embryonic mouse lung morphogenesis; 2) To determine the respective functional specificity of mspry2&4 to negatively modulate mouse respiratory morphogenesis; 3) To determine whether mspry2 functions as an FGF ligand protein or binds candidate signaling proteins in the Ras pathway, and to determine which domains of mspry2 mediate these specific protein-protein functional interactions using mutational analysis; 4) To identify transcriptional control elements regulating spatial localization of mspry2 during lung branching morphogenesis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044977-12
Application #
6638303
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Berberich, Mary Anne
Project Start
1991-08-01
Project End
2005-01-04
Budget Start
2003-04-01
Budget End
2005-01-04
Support Year
12
Fiscal Year
2003
Total Cost
$365,625
Indirect Cost
Name
University of Southern California
Department
Dentistry
Type
Schools of Dentistry
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
El-Hashash, Ahmed H K; Turcatel, Gianluca; Varma, Saaket et al. (2012) Eya1 protein phosphatase regulates tight junction formation in lung distal epithelium. J Cell Sci 125:4036-48
Turcatel, Gianluca; Rubin, Nicole; El-Hashash, Ahmed et al. (2012) MIR-99a and MIR-99b modulate TGF-* induced epithelial to mesenchymal plasticity in normal murine mammary gland cells. PLoS One 7:e31032
El-Hashash, Ahmed H K; Warburton, David (2012) Numb expression and asymmetric versus symmetric cell division in distal embryonic lung epithelium. J Histochem Cytochem 60:675-82
El-Hashash, Ahmed H; Warburton, David (2011) Cell polarity and spindle orientation in the distal epithelium of embryonic lung. Dev Dyn 240:441-5
El-Hashash, Ahmed H K; Turcatel, Gianluca; Al Alam, Denise et al. (2011) Eya1 controls cell polarity, spindle orientation, cell fate and Notch signaling in distal embryonic lung epithelium. Development 138:1395-407
Sala, Frederic G; Del Moral, Pierre-Marie; Tiozzo, Caterina et al. (2011) FGF10 controls the patterning of the tracheal cartilage rings via Shh. Development 138:273-82
Jackson, Sha-Ron; Lee, Jooeun; Reddy, Raghava et al. (2011) Partial pneumonectomy of telomerase null mice carrying shortened telomeres initiates cell growth arrest resulting in a limited compensatory growth response. Am J Physiol Lung Cell Mol Physiol 300:L898-909
El-Hashash, Ahmed H K; Al Alam, Denise; Turcatel, Gianluca et al. (2011) Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung. Dev Biol 353:242-58
El-Hashash, Ahmed H K; Al Alam, Denise; Turcatel, Gianluca et al. (2011) Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung. Dev Biol 350:112-26
Tarantal, A F; Chen, H; Shi, T T et al. (2010) Overexpression of transforming growth factor-beta1 in fetal monkey lung results in prenatal pulmonary fibrosis. Eur Respir J 36:907-14

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