MC Williams, Y Cao, A Hinds, AK Rishi and A Wetterwald
Department of Medicine, Boston University School of Medicine, Massachusetts, USA.

T1 alpha is the first marker gene known to be expressed in the adult lung solely by the alveolar type I epithelial cell. Previous studies showed that T1 alpha transcripts are abundant in early rat embryos where they are found in the nervous system and in the foregut and certain of its derivatives including the primitive lung. By mid- to late gestation T1 alpha messenger RNA (mRNA) expression is lost from neural tissues but appears to increase in the lung throughout fetal life. To determine whether the T1 alpha transcripts are translated into protein, especially in early embryos which sometimes express transcripts that are translationally silent, we performed immunohistochemistry on embryos and fetal tissues and analyzed certain tissues by western blotting using a monoclonal antibody against T1 alpha protein. T1 alpha protein is present at all sites that have previously been shown to express the mRNA and at similar developmental stages. As estimated from western blots, T1 alpha protein abundance peaks at about fetal day 16 in the brain and decreases thereafter to a relative level in the adult that is lower than that of the neural tube of the day 13 embryo. Relative protein abundance in the lung is very low, although detectable, on embryonic day 13 but increases slowly until fetal day 20 when there is a dramatic increase. At the time of birth, restriction to the type I cell is not complete and therefore must occur during postnatal lung development. Immunostaining reveals additional sites of expression in fetal and adult rats that had not been clearly visualized in previous in situ hybridization studies. T1 alpha is present in mesonephric tubules and apparently in primitive germ cells but is not detectable in specific cells in the adult kidney, ovary, or testis. However, cells of the choroid plexus of the central nervous system and the ciliary epithelium of the eye express T1 alpha in both fetuses and adults. The well-known functions of these epithelia are to elaborate cerebrospinal fluid and aqueous humor respectively by processes of active ion transport and water fluxes, probably through the aquaporin 1 (channel-forming integral membrane protein [CHIP] 28). We speculate therefore that T1 alpha protein may modulate or participate in these types of cellular functions in the lung.

This article has been cited by other articles:

				L. Cakarova, L. M. Marsh, J. Wilhelm, K. Mayer, F. Grimminger, W. Seeger, J. Lohmeyer, and S. Herold Macrophage Tumor Necrosis Factor-{alpha} Induces Epithelial Expression of Granulocyte-Macrophage Colony-stimulating Factor: Impact on Alveolar Epithelial Repair Am. J. Respir. Crit. Care Med., September 15, 2009; 180(6): 521 - 532. [Abstract] [Full Text] [PDF]

				A. Navarro, R. E. Perez, M. Rezaiekhaligh, S. M. Mabry, and I. I. Ekekezie T1{alpha}/podoplanin is essential for capillary morphogenesis in lymphatic endothelial cells Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L543 - L551. [Abstract] [Full Text] [PDF]

				E. L. Herzog, A. R. Brody, T. V. Colby, R. Mason, and M. C. Williams Knowns and Unknowns of the Alveolus Proceedings of the ATS, September 15, 2008; 5(7): 778 - 782. [Abstract] [Full Text] [PDF]

				J. N. Vanderbilt, L. Allen, R. F. Gonzalez, Z. Tigue, J. Edmondson, D. Ansaldi, A. M. Gillespie, and L. G. Dobbs Directed Expression of Transgenes to Alveolar Type I Cells in the Mouse Am. J. Respir. Cell Mol. Biol., September 1, 2008; 39(3): 253 - 262. [Abstract] [Full Text] [PDF]

				R. Qiao, W. Yan, C. Clavijo, R. Mehrian-Shai, Q. Zhong, K.-J. Kim, D. Ann, E. D. Crandall, and Z. Borok Effects of KGF on Alveolar Epithelial Cell Transdifferentiation Are Mediated by JNK Signaling Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 239 - 246. [Abstract] [Full Text] [PDF]

				E. Martin-Villar, D. Megias, S. Castel, M. M. Yurrita, S. Vilaro, and M. Quintanilla Podoplanin binds ERM proteins to activate RhoA and promote epithelial-mesenchymal transition J. Cell Sci., November 1, 2006; 119(21): 4541 - 4553. [Abstract] [Full Text] [PDF]

				T. Weng, Z. Chen, N. Jin, L. Gao, and L. Liu Gene expression profiling identifies regulatory pathways involved in the late stage of rat fetal lung development Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1027 - L1037. [Abstract] [Full Text] [PDF]

				V. Schacht, S. S. Dadras, L. A. Johnson, D. G. Jackson, Y.-K. Hong, and M. Detmar Up-Regulation of the Lymphatic Marker Podoplanin, a Mucin-Type Transmembrane Glycoprotein, in Human Squamous Cell Carcinomas and Germ Cell Tumors Am. J. Pathol., March 1, 2005; 166(3): 913 - 921. [Abstract] [Full Text] [PDF]

				M.C. McElroy and M. Kasper The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair Eur. Respir. J., October 1, 2004; 24(4): 664 - 673. [Abstract] [Full Text] [PDF]

				K. Dahlin, E. M. Mager, L. Allen, Z. Tigue, L. Goodglick, M. Wadehra, and L. Dobbs Identification of Genes Differentially Expressed in Rat Alveolar Type I Cells Am. J. Respir. Cell Mol. Biol., September 1, 2004; 31(3): 309 - 316. [Abstract] [Full Text] [PDF]

				M. Shirasawa, N. Fujiwara, S. Hirabayashi, H. Ohno, J. Iida, K. Makita, and Y. Hata Receptor for advanced glycation end-products is a marker of type I lung alveolar cells Genes Cells, February 1, 2004; 9(2): 165 - 174. [Abstract] [Full Text] [PDF]

				R. Qiao, B. Zhou, J. M. Liebler, X. Li, E. D. Crandall, and Z. Borok Identification of Three Genes of Known Function Expressed by Alveolar Epithelial Type I Cells Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 98 - 105. [Abstract] [Full Text] [PDF]

				J. A. Gutierrez, V. V. Suzara, and L. G. Dobbs Continuous Mechanical Contraction Modulates Expression of Alveolar Epithelial Cell Phenotype Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 81 - 87. [Abstract] [Full Text] [PDF]

				M. Koval Sharing signals: connecting lung epithelial cells with gap junction channels Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L875 - L893. [Abstract] [Full Text] [PDF]

				C. Galambos, Y.-S. Ng, A. Ali, A. Noguchi, S. Lovejoy, P. A. D'Amore, and D. E. deMello Defective Pulmonary Development in the Absence of Heparin-Binding Vascular Endothelial Growth Factor Isoforms Am. J. Respir. Cell Mol. Biol., August 1, 2002; 27(2): 194 - 203. [Abstract] [Full Text] [PDF]

				M. I. Ramirez, L. Pollack, G. Millien, Y. X. Cao, A. Hinds, and M. C. Williams The {alpha}-Isoform of Caveolin-1 Is a Marker of Vasculogenesis in Early Lung Development J. Histochem. Cytochem., January 1, 2002; 50(1): 33 - 42. [Abstract] [Full Text]

				D. N. Kotton, B. Y. Ma, W. V. Cardoso, E. A. Sanderson, R. S. Summer, M. C. Williams, and A. Fine Bone marrow-derived cells as progenitors of lung alveolar epithelium Development, December 15, 2001; 128(24): 5181 - 5188. [Abstract] [Full Text] [PDF]

				G. M. Boylan, J. G. Pryde, L. G. Dobbs, and M. C. McElroy Identification of a novel antigen on the apical surface of rat alveolar epithelial type II and Clara cells Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1318 - L1326. [Abstract] [Full Text] [PDF]

				E. D. CRANDALL and M. A. MATTHAY Alveolar Epithelial Transport . Basic Science to Clinical Medicine Am. J. Respir. Crit. Care Med., March 15, 2001; 163(4): 1021 - 1029. [Full Text]

				Z.-Y. Li, K. Hirayoshi, and Y. Suzuki Expression of N-deacetylase/sulfotransferase and 3-O-sulfotransferase in rat alveolar type II cells Am J Physiol Lung Cell Mol Physiol, August 1, 2000; 279(2): L292 - L301. [Abstract] [Full Text] [PDF]

				A. S. Verkman, M. A. Matthay, and Y. Song Aquaporin water channels and lung physiology Am J Physiol Lung Cell Mol Physiol, May 1, 2000; 278(5): L867 - L879. [Abstract] [Full Text] [PDF]

				F. Scholl, C Gamallo, S Vilar?o, and M Quintanilla Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes J. Cell Sci., January 12, 1999; 112(24): 4601 - 4613. [Abstract] [PDF]

				M Weaver, J. Yingling, N. Dunn, S Bellusci, and B. Hogan Bmp signaling regulates proximal-distal differentiation of endoderm in mouse lung development Development, January 9, 1999; 126(18): 4005 - 4015. [Abstract] [PDF]

				J. N. Vanderbilt and L. G. Dobbs Characterization of the Gene and Promoter for RTI40, a Differentiation Marker of Type I Alveolar Epithelial Cells Am. J. Respir. Cell Mol. Biol., October 1, 1998; 19(4): 662 - 671. [Abstract] [Full Text]

				T. Ma, B. Yang, M. A. Matthay, and A. S. Verkman Evidence against a Role of Mouse, Rat, and Two Cloned Human T1alpha Isoforms as a Water Channel or a Regulator of Aquaporin-type Water Channels Am. J. Respir. Cell Mol. Biol., July 1, 1998; 19(1): 143 - 149. [Abstract] [Full Text]

				Z. Borok, S. I. Danto, R. L. Lubman, Y. Cao, M. C. Williams, and E. D. Crandall Modulation of T1alpha expression with alveolar epithelial cell phenotype in vitro Am J Physiol Lung Cell Mol Physiol, July 1, 1998; 275(1): L155 - L164. [Abstract] [Full Text] [PDF]

				L. G. Dobbs, R. Gonzalez, M. A. Matthay, E. P. Carter, L. Allen, and A. S. Verkman Highly water-permeable type I alveolar epithelial cells confer high water permeability between the airspace and vasculature in rat lung PNAS, March 17, 1998; 95(6): 2991 - 2996. [Abstract] [Full Text] [PDF]

				M. C. McElroy, J.-F. Pittet, L. Allen, J. P. Wiener-Kronish, and L. G. Dobbs Biochemical detection of type I cell damage after nitrogen dioxide-induced lung injury in rats Am J Physiol Lung Cell Mol Physiol, December 1, 1997; 273(6): L1228 - L1234. [Abstract] [Full Text] [PDF]

				M. I. Ramirez, A. K. Rishi, Y. X. Cao, and M. C. Williams TGT3, Thyroid Transcription Factor I, and Sp1 Elements Regulate Transcriptional Activity of the 1.3-Kilobase Pair Promoter of T1alpha , a Lung Alveolar Type I Cell Gene J. Biol. Chem., October 17, 1997; 272(42): 26285 - 26294. [Abstract] [Full Text] [PDF]