| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Molecular Genetics, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA
2 Department of Molecular Genetics, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA; Shemyakin Institute of Bioorganic Chemistry, Moscow, Russian Federation
3 Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, OH, USA
4 Shemyakin Institute of Bioorganic Chemistry, Moscow, Russian Federation
* To whom correspondence should be addressed. E-mail: vkalin{at}uic.edu.
The Forkhead Box f1 (Foxf1) transcription factor is expressed in the mouse splanchnic (visceral) mesoderm, which contributes to development of liver, gall bladder, lung, and intestinal tract. Pulmonary hemorrhage and peripheral microvasculature defects were found in approximately half of the newborn Foxf1 +/- mice that expressed low levels of lung Foxf1 mRNA (Low Foxf1 +/- mice). Interestingly, normal microvascular development was found in the surviving newborn High Foxf1 +/- mice, which compensated for pulmonary Foxf1 haploinsufficiency and expressed wild type (WT) Foxf1 levels. To identify expression of genes regulated by Foxf1, we used Affymetrix microarrays to determine embryonic lung RNAs influenced by Foxf1 haploinsufficiency. Embryonic Foxf1 +/- lungs exhibited diminished expression of Hepatocyte Growth Factor receptor c-met, Myosin VI, the transcription factors SP-3, BMI-1, ATF-2, and glucocorticoid receptor, and cell cycle inhibitors p53, p21Cip1, retinoblastoma and p107. Furthermore, Notch-2 signaling was decreased in embryonic Foxf1 +/- lungs as evidenced by significantly reduced levels of the Notch-2 receptor and the Notch-2 downstream target Hairy-enhancer of Split 1 (Hes-1). The severity of the Notch-2 signaling defect in 18 dpc Foxf1 +/- lungs correlated with Foxf1 mRNA levels. Disruption of pulmonary Notch-2 signaling continued in newborn Low Foxf1 +/- mice, which died of lung hemorrhage and failed to compensate for Foxf1 haploinsufficiency. In contrast, newborn High Foxf1 +/- lungs restored WT levels of Notch-2 signaling, which was associated with normal microvascular formation and survival. Foxf1 haploinsufficiency disrupted pulmonary expression of genes in the Notch-2 signaling pathway and resulted in abnormal development of lung microvasculature.
This article has been cited by other articles:
|
|
 |
|
  J. B. Samon, A. Champhekar, L. M. Minter, J. C. Telfer, L. Miele, A. Fauq, P. Das, T. E. Golde, and B. A. Osborne Notch1 and TGF{beta}1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells Blood, September 1, 2008; 112(5): 1813 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. N. Papanicolaou, Y. Izumiya, and K. Walsh Forkhead Transcription Factors and Cardiovascular Biology Circ. Res., January 4, 2008; 102(1): 16 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. D. Hardie, T. R. Korfhagen, M. A. Sartor, A. Prestridge, M. Medvedovic, T. D. Le Cras, M. Ikegami, S. C. Wesselkamper, C. Davidson, M. Dietsch, et al. Genomic Profile of Matrix and Vasculature Remodeling in TGF-{alpha} Induced Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 309 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Maeda, V. Dave, and J. A. Whitsett Transcriptional Control of Lung Morphogenesis Physiol Rev, January 1, 2007; 87(1): 219 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rojas, S. De Val, A. B. Heidt, S.-M. Xu, J. Bristow, and B. L. Black Gata4 expression in lateral mesoderm is downstream of BMP4 and is activated directly by Forkhead and GATA transcription factors through a distal enhancer element Development, August 1, 2005; 132(15): 3405 - 3417. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
