Hepatocyte nuclear factor 3/fork head homolog 11 is expressed in proliferating epithelial and mesenchymal cells of embryonic and adult tissues (original) (raw)

Abstract

The hepatocyte nuclear factor 3alpha (HNF-3alpha) and 3beta proteins have homology in the winged helix/fork head DNA binding domain and regulate cell-specific transcription in hepatocytes and in respiratory and intestinal epithelia. In this study, we describe two novel isoforms of the winged helix transcription factor family, HNF-3/fork head homolog 11A (HFH-11A) and HFH-11B, isolated from the human colon carcinoma HT-29 cell line. We show that these isoforms arise via differential splicing and are expressed in a number of epithelial cell lines derived from tumors (HT-29, Caco-2, HepG2, HeLa, A549, and H441). We demonstrate that differentiation of Caco-2 cells toward the enterocyte lineage results in decreased HFH-11 expression and reciprocal increases in HNF-3alpha and HNF-3beta mRNA levels. In situ hybridization of 16 day postcoitus mouse embryos demonstrates that HFH-11 expression is found in the mesenchymal and epithelial cells of the liver, lung, intestine, renal cortex, and urinary tract. Although HFH-11 exhibits a wide cellular expression pattern in the embryo, its adult expression pattern is restricted to epithelial cells of Lieberkühn's crypts of the intestine, the spermatocytes and spermatids of the testis, and the thymus and colon. HFH-11 expression is absent in adult hepatocytes, but its expression is reactivated in proliferating hepatocytes at 4, 24, and 48 h after partial hepatectomy. Consistent with these findings, we demonstrate that HFH-11 mRNA levels are stimulated by intratracheal administration of keratinocyte growth factor in adult lung and its expression in an adult endothelial cell line is reactivated in response to oxidative stress. These experiments show that the HFH-11 transcription factor is expressed in embryonic mesenchymal and epithelial cells and its expression is reactivated in these adult cell types by proliferative signals or oxidative stress.

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  1. Abe J., Kusuhara M., Ulevitch R. J., Berk B. C., Lee J. D. Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase. J Biol Chem. 1996 Jul 12;271(28):16586–16590. doi: 10.1074/jbc.271.28.16586. [DOI] [PubMed] [Google Scholar]
  2. Ang S. L., Rossant J. HNF-3 beta is essential for node and notochord formation in mouse development. Cell. 1994 Aug 26;78(4):561–574. doi: 10.1016/0092-8674(94)90522-3. [DOI] [PubMed] [Google Scholar]
  3. Ang S. L., Wierda A., Wong D., Stevens K. A., Cascio S., Rossant J., Zaret K. S. The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development. 1993 Dec;119(4):1301–1315. doi: 10.1242/dev.119.4.1301. [DOI] [PubMed] [Google Scholar]
  4. Bard J. B. The development of the mouse kidney--embryogenesis writ small. Curr Opin Genet Dev. 1992 Aug;2(4):589–595. doi: 10.1016/s0959-437x(05)80177-7. [DOI] [PubMed] [Google Scholar]
  5. Bisaha J. G., Simon T. C., Gordon J. I., Breslow J. L. Characterization of an enhancer element in the human apolipoprotein C-III gene that regulates human apolipoprotein A-I gene expression in the intestinal epithelium. J Biol Chem. 1995 Aug 25;270(34):19979–19988. doi: 10.1074/jbc.270.34.19979. [DOI] [PubMed] [Google Scholar]
  6. Blackwood E. M., Eisenman R. N. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. doi: 10.1126/science.2006410. [DOI] [PubMed] [Google Scholar]
  7. Bohinski R. J., Di Lauro R., Whitsett J. A. The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis. Mol Cell Biol. 1994 Sep;14(9):5671–5681. doi: 10.1128/mcb.14.9.5671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bry L., Falk P., Huttner K., Ouellette A., Midtvedt T., Gordon J. I. Paneth cell differentiation in the developing intestine of normal and transgenic mice. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10335–10339. doi: 10.1073/pnas.91.22.10335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Caelles C., Hennemann H., Karin M. M-phase-specific phosphorylation of the POU transcription factor GHF-1 by a cell cycle-regulated protein kinase inhibits DNA binding. Mol Cell Biol. 1995 Dec;15(12):6694–6701. doi: 10.1128/mcb.15.12.6694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chandrasekaran C., Gordon J. I. Cell lineage-specific and differentiation-dependent patterns of CCAAT/enhancer binding protein alpha expression in the gut epithelium of normal and transgenic mice. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8871–8875. doi: 10.1073/pnas.90.19.8871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chantret I., Barbat A., Dussaulx E., Brattain M. G., Zweibaum A. Epithelial polarity, villin expression, and enterocytic differentiation of cultured human colon carcinoma cells: a survey of twenty cell lines. Cancer Res. 1988 Apr 1;48(7):1936–1942. [PubMed] [Google Scholar]
  12. Clark-Lewis I., Sanghera J. S., Pelech S. L. Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis-activated myelin basic protein kinase. J Biol Chem. 1991 Aug 15;266(23):15180–15184. [PubMed] [Google Scholar]
  13. Clark K. L., Halay E. D., Lai E., Burley S. K. Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature. 1993 Jul 29;364(6436):412–420. doi: 10.1038/364412a0. [DOI] [PubMed] [Google Scholar]
  14. Clevidence D. E., Overdier D. G., Peterson R. S., Porcella A., Ye H., Paulson K. E., Costa R. H. Members of the HNF-3/forkhead family of transcription factors exhibit distinct cellular expression patterns in lung and regulate the surfactant protein B promoter. Dev Biol. 1994 Nov;166(1):195–209. doi: 10.1006/dbio.1994.1307. [DOI] [PubMed] [Google Scholar]
  15. Clevidence D. E., Overdier D. G., Tao W., Qian X., Pani L., Lai E., Costa R. H. Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3948–3952. doi: 10.1073/pnas.90.9.3948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cohn S. M., Simon T. C., Roth K. A., Birkenmeier E. H., Gordon J. I. Use of transgenic mice to map cis-acting elements in the intestinal fatty acid binding protein gene (Fabpi) that control its cell lineage-specific and regional patterns of expression along the duodenal-colonic and crypt-villus axes of the gut epithelium. J Cell Biol. 1992 Oct;119(1):27–44. doi: 10.1083/jcb.119.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Costa R. H., Grayson D. R., Darnell J. E., Jr Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes. Mol Cell Biol. 1989 Apr;9(4):1415–1425. doi: 10.1128/mcb.9.4.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Davies J. How to build a kidney. Semin Cell Biol. 1993 Jun;4(3):213–219. doi: 10.1006/scel.1993.1025. [DOI] [PubMed] [Google Scholar]
  19. Deng T., Karin M. c-Fos transcriptional activity stimulated by H-Ras-activated protein kinase distinct from JNK and ERK. Nature. 1994 Sep 8;371(6493):171–175. doi: 10.1038/371171a0. [DOI] [PubMed] [Google Scholar]
  20. DiPersio C. M., Jackson D. A., Zaret K. S. The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology. Mol Cell Biol. 1991 Sep;11(9):4405–4414. doi: 10.1128/mcb.11.9.4405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Doğan A., Wang Z. D., Spencer J. E-cadherin expression in intestinal epithelium. J Clin Pathol. 1995 Feb;48(2):143–146. doi: 10.1136/jcp.48.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Duncan S. A., Manova K., Chen W. S., Hoodless P., Weinstein D. C., Bachvarova R. F., Darnell J. E., Jr Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7598–7602. doi: 10.1073/pnas.91.16.7598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Fausto N., Laird A. D., Webber E. M. Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration. FASEB J. 1995 Dec;9(15):1527–1536. doi: 10.1096/fasebj.9.15.8529831. [DOI] [PubMed] [Google Scholar]
  24. Fishel R., Lescoe M. K., Rao M. R., Copeland N. G., Jenkins N. A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027–1038. doi: 10.1016/0092-8674(93)90546-3. [DOI] [PubMed] [Google Scholar]
  25. Flodby P., Antonson P., Barlow C., Blanck A., Porsch-Hällström I., Xanthopoulos K. G. Differential patterns of expression of three C/EBP isoforms, HNF-1, and HNF-4 after partial hepatectomy in rats. Exp Cell Res. 1993 Sep;208(1):248–256. doi: 10.1006/excr.1993.1244. [DOI] [PubMed] [Google Scholar]
  26. Gartel A. L., Serfas M. S., Gartel M., Goufman E., Wu G. S., el-Deiry W. S., Tyner A. L. p21 (WAF1/CIP1) expression is induced in newly nondividing cells in diverse epithelia and during differentiation of the Caco-2 intestinal cell line. Exp Cell Res. 1996 Sep 15;227(2):171–181. doi: 10.1006/excr.1996.0264. [DOI] [PubMed] [Google Scholar]
  27. Ginsburg G. S., Ozer J., Karathanasis S. K. Intestinal apolipoprotein AI gene transcription is regulated by multiple distinct DNA elements and is synergistically activated by the orphan nuclear receptor, hepatocyte nuclear factor 4. J Clin Invest. 1995 Jul;96(1):528–538. doi: 10.1172/JCI118065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Guyton K. Z., Liu Y., Gorospe M., Xu Q., Holbrook N. J. Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem. 1996 Feb 23;271(8):4138–4142. doi: 10.1074/jbc.271.8.4138. [DOI] [PubMed] [Google Scholar]
  29. Hackett B. P., Brody S. L., Liang M., Zeitz I. D., Bruns L. A., Gitlin J. D. Primary structure of hepatocyte nuclear factor/forkhead homologue 4 and characterization of gene expression in the developing respiratory and reproductive epithelium. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4249–4253. doi: 10.1073/pnas.92.10.4249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Harnish D. C., Malik S., Karathanasis S. K. Activation of apolipoprotein AI gene transcription by the liver-enriched factor HNF-3. J Biol Chem. 1994 Nov 11;269(45):28220–28226. [PubMed] [Google Scholar]
  31. Hatini V., Huh S. O., Herzlinger D., Soares V. C., Lai E. Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF-2. Genes Dev. 1996 Jun 15;10(12):1467–1478. doi: 10.1101/gad.10.12.1467. [DOI] [PubMed] [Google Scholar]
  32. Hermiston M. L., Wong M. H., Gordon J. I. Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for nonautonomous regulation of cell fate in a self-renewing system. Genes Dev. 1996 Apr 15;10(8):985–996. doi: 10.1101/gad.10.8.985. [DOI] [PubMed] [Google Scholar]
  33. Hromas R., Costa R. The hepatocyte nuclear factor-3/forkhead transcription regulatory family in development, inflammation, and neoplasia. Crit Rev Oncol Hematol. 1995 Aug;20(1-2):129–140. doi: 10.1016/1040-8428(94)00151-i. [DOI] [PubMed] [Google Scholar]
  34. Ikeda K., Shaw-White J. R., Wert S. E., Whitsett J. A. Hepatocyte nuclear factor 3 activates transcription of thyroid transcription factor 1 in respiratory epithelial cells. Mol Cell Biol. 1996 Jul;16(7):3626–3636. doi: 10.1128/mcb.16.7.3626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jacob A., Budhiraja S., Qian X., Clevidence D., Costa R. H., Reichel R. R. Retinoic acid-mediated activation of HNF-3 alpha during EC stem cell differentiation. Nucleic Acids Res. 1994 Jun 11;22(11):2126–2133. doi: 10.1093/nar/22.11.2126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. James R., Erler T., Kazenwadel J. Structure of the murine homeobox gene cdx-2. Expression in embryonic and adult intestinal epithelium. J Biol Chem. 1994 May 27;269(21):15229–15237. [PubMed] [Google Scholar]
  37. Kaestner K. H., Hiemisch H., Luckow B., Schütz G. The HNF-3 gene family of transcription factors in mice: gene structure, cDNA sequence, and mRNA distribution. Genomics. 1994 Apr;20(3):377–385. doi: 10.1006/geno.1994.1191. [DOI] [PubMed] [Google Scholar]
  38. Karin M. The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem. 1995 Jul 14;270(28):16483–16486. doi: 10.1074/jbc.270.28.16483. [DOI] [PubMed] [Google Scholar]
  39. Kimura S., Hara Y., Pineau T., Fernandez-Salguero P., Fox C. H., Ward J. M., Gonzalez F. J. The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev. 1996 Jan 1;10(1):60–69. doi: 10.1101/gad.10.1.60. [DOI] [PubMed] [Google Scholar]
  40. Knowles B. B., Howe C. C., Aden D. P. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980 Jul 25;209(4455):497–499. doi: 10.1126/science.6248960. [DOI] [PubMed] [Google Scholar]
  41. Kuo C. J., Conley P. B., Chen L., Sladek F. M., Darnell J. E., Jr, Crabtree G. R. A transcriptional hierarchy involved in mammalian cell-type specification. Nature. 1992 Jan 30;355(6359):457–461. doi: 10.1038/355457a0. [DOI] [PubMed] [Google Scholar]
  42. Lai E., Prezioso V. R., Tao W. F., Chen W. S., Darnell J. E., Jr Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. Genes Dev. 1991 Mar;5(3):416–427. doi: 10.1101/gad.5.3.416. [DOI] [PubMed] [Google Scholar]
  43. Li L., Zhou J., James G., Heller-Harrison R., Czech M. P., Olson E. N. FGF inactivates myogenic helix-loop-helix proteins through phosphorylation of a conserved protein kinase C site in their DNA-binding domains. Cell. 1992 Dec 24;71(7):1181–1194. doi: 10.1016/s0092-8674(05)80066-2. [DOI] [PubMed] [Google Scholar]
  44. Loyer P., Glaise D., Cariou S., Baffet G., Meijer L., Guguen-Guillouzo C. Expression and activation of cdks (1 and 2) and cyclins in the cell cycle progression during liver regeneration. J Biol Chem. 1994 Jan 28;269(4):2491–2500. [PubMed] [Google Scholar]
  45. Mietus-Snyder M., Sladek F. M., Ginsburg G. S., Kuo C. F., Ladias J. A., Darnell J. E., Jr, Karathanasis S. K. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol Cell Biol. 1992 Apr;12(4):1708–1718. doi: 10.1128/mcb.12.4.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Monaghan A. P., Kaestner K. H., Grau E., Schütz G. Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. Development. 1993 Nov;119(3):567–578. doi: 10.1242/dev.119.3.567. [DOI] [PubMed] [Google Scholar]
  47. Moreno S., Nurse P. Substrates for p34cdc2: in vivo veritas? Cell. 1990 May 18;61(4):549–551. doi: 10.1016/0092-8674(90)90463-o. [DOI] [PubMed] [Google Scholar]
  48. Nehls M., Pfeifer D., Schorpp M., Hedrich H., Boehm T. New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature. 1994 Nov 3;372(6501):103–107. doi: 10.1038/372103a0. [DOI] [PubMed] [Google Scholar]
  49. Overdier D. G., Porcella A., Costa R. H. The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Mol Cell Biol. 1994 Apr;14(4):2755–2766. doi: 10.1128/mcb.14.4.2755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Pani L., Overdier D. G., Porcella A., Qian X., Lai E., Costa R. H. Hepatocyte nuclear factor 3 beta contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein. Mol Cell Biol. 1992 Sep;12(9):3723–3732. doi: 10.1128/mcb.12.9.3723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Parker S. B., Eichele G., Zhang P., Rawls A., Sands A. T., Bradley A., Olson E. N., Harper J. W., Elledge S. J. p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science. 1995 Feb 17;267(5200):1024–1027. doi: 10.1126/science.7863329. [DOI] [PubMed] [Google Scholar]
  52. Potten C. S., Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development. 1990 Dec;110(4):1001–1020. doi: 10.1242/dev.110.4.1001. [DOI] [PubMed] [Google Scholar]
  53. Qian X., Costa R. H. Analysis of hepatocyte nuclear factor-3 beta protein domains required for transcriptional activation and nuclear targeting. Nucleic Acids Res. 1995 Apr 11;23(7):1184–1191. doi: 10.1093/nar/23.7.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Qian X., Samadani U., Porcella A., Costa R. H. Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription. Mol Cell Biol. 1995 Mar;15(3):1364–1376. doi: 10.1128/mcb.15.3.1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Rechsteiner M., Rogers S. W. PEST sequences and regulation by proteolysis. Trends Biochem Sci. 1996 Jul;21(7):267–271. [PubMed] [Google Scholar]
  56. Reisher S. R., Hughes T. E., Ordovas J. M., Schaefer E. J., Feinstein S. I. Increased expression of apolipoprotein genes accompanies differentiation in the intestinal cell line Caco-2. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5757–5761. doi: 10.1073/pnas.90.12.5757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Ruiz i Altaba A., Prezioso V. R., Darnell J. E., Jessell T. M. Sequential expression of HNF-3 beta and HNF-3 alpha by embryonic organizing centers: the dorsal lip/node, notochord and floor plate. Mech Dev. 1993 Dec;44(2-3):91–108. doi: 10.1016/0925-4773(93)90060-b. [DOI] [PubMed] [Google Scholar]
  58. Sasaki H., Hogan B. L. Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. Development. 1993 May;118(1):47–59. doi: 10.1242/dev.118.1.47. [DOI] [PubMed] [Google Scholar]
  59. Sawaya P. L., Stripp B. R., Whitsett J. A., Luse D. S. The lung-specific CC10 gene is regulated by transcription factors from the AP-1, octamer, and hepatocyte nuclear factor 3 families. Mol Cell Biol. 1993 Jul;13(7):3860–3871. doi: 10.1128/mcb.13.7.3860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Serfas M. S., Tyner A. L. HNF-1 alpha and HNF-1 beta expression in mouse intestinal crypts. Am J Physiol. 1993 Sep;265(3 Pt 1):G506–G513. doi: 10.1152/ajpgi.1993.265.3.G506. [DOI] [PubMed] [Google Scholar]
  61. Simon T. C., Roth K. A., Gordon J. I. Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. J Biol Chem. 1993 Aug 25;268(24):18345–18358. [PubMed] [Google Scholar]
  62. Suh E., Chen L., Taylor J., Traber P. G. A homeodomain protein related to caudal regulates intestine-specific gene transcription. Mol Cell Biol. 1994 Nov;14(11):7340–7351. doi: 10.1128/mcb.14.11.7340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Suh E., Traber P. G. An intestine-specific homeobox gene regulates proliferation and differentiation. Mol Cell Biol. 1996 Feb;16(2):619–625. doi: 10.1128/mcb.16.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Taraviras S., Monaghan A. P., Schütz G., Kelsey G. Characterization of the mouse HNF-4 gene and its expression during mouse embryogenesis. Mech Dev. 1994 Nov;48(2):67–79. doi: 10.1016/0925-4773(94)90017-5. [DOI] [PubMed] [Google Scholar]
  65. Taub R. Liver regeneration 4: transcriptional control of liver regeneration. FASEB J. 1996 Mar;10(4):413–427. [PubMed] [Google Scholar]
  66. Theill L. E., Hattori K., Lazzaro D., Castrillo J. L., Karin M. Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins. EMBO J. 1992 Jun;11(6):2261–2269. doi: 10.1002/j.1460-2075.1992.tb05285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Thomas G. MAP kinase by any other name smells just as sweet. Cell. 1992 Jan 10;68(1):3–6. doi: 10.1016/0092-8674(92)90199-m. [DOI] [PubMed] [Google Scholar]
  68. Traber P. G. Differentiation of intestinal epithelial cells: lessons from the study of intestine-specific gene expression. J Lab Clin Med. 1994 Apr;123(4):467–477. [PubMed] [Google Scholar]
  69. Tyner A. L., Godbout R., Compton R. S., Tilghman S. M. The ontogeny of alpha-fetoprotein gene expression in the mouse gastrointestinal tract. J Cell Biol. 1990 Apr;110(4):915–927. doi: 10.1083/jcb.110.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Ulich T. R., Yi E. S., Longmuir K., Yin S., Biltz R., Morris C. F., Housley R. M., Pierce G. F. Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo. J Clin Invest. 1994 Mar;93(3):1298–1306. doi: 10.1172/JCI117086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Weigel D., Jäckle H. The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell. 1990 Nov 2;63(3):455–456. doi: 10.1016/0092-8674(90)90439-l. [DOI] [PubMed] [Google Scholar]
  72. Weinstein D. C., Ruiz i Altaba A., Chen W. S., Hoodless P., Prezioso V. R., Jessell T. M., Darnell J. E., Jr The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo. Cell. 1994 Aug 26;78(4):575–588. doi: 10.1016/0092-8674(94)90523-1. [DOI] [PubMed] [Google Scholar]
  73. Westendorf J. M., Rao P. N., Gerace L. Cloning of cDNAs for M-phase phosphoproteins recognized by the MPM2 monoclonal antibody and determination of the phosphorylated epitope. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):714–718. doi: 10.1073/pnas.91.2.714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Wice B. M., Gordon J. I. A strategy for isolation of cDNAs encoding proteins affecting human intestinal epithelial cell growth and differentiation: characterization of a novel gut-specific N-myristoylated annexin. J Cell Biol. 1992 Jan;116(2):405–422. doi: 10.1083/jcb.116.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Wilson T. M., Ewel A., Duguid J. R., Eble J. N., Lescoe M. K., Fishel R., Kelley M. R. Differential cellular expression of the human MSH2 repair enzyme in small and large intestine. Cancer Res. 1995 Nov 15;55(22):5146–5150. [PubMed] [Google Scholar]
  76. Wu G. D., Chen L., Forslund K., Traber P. G. Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and HNF-1 beta regulate transcription via two elements in an intestine-specific promoter. J Biol Chem. 1994 Jun 24;269(25):17080–17085. [PubMed] [Google Scholar]
  77. Wu H., Wade M., Krall L., Grisham J., Xiong Y., Van Dyke T. Targeted in vivo expression of the cyclin-dependent kinase inhibitor p21 halts hepatocyte cell-cycle progression, postnatal liver development and regeneration. Genes Dev. 1996 Feb 1;10(3):245–260. doi: 10.1101/gad.10.3.245. [DOI] [PubMed] [Google Scholar]
  78. Xuan S., Baptista C. A., Balas G., Tao W., Soares V. C., Lai E. Winged helix transcription factor BF-1 is essential for the development of the cerebral hemispheres. Neuron. 1995 Jun;14(6):1141–1152. doi: 10.1016/0896-6273(95)90262-7. [DOI] [PubMed] [Google Scholar]
  79. Zaret K. S. Molecular genetics of early liver development. Annu Rev Physiol. 1996;58:231–251. doi: 10.1146/annurev.ph.58.030196.001311. [DOI] [PubMed] [Google Scholar]
  80. Zhou L., Lim L., Costa R. H., Whitsett J. A. Thyroid transcription factor-1, hepatocyte nuclear factor-3beta, surfactant protein B, C, and Clara cell secretory protein in developing mouse lung. J Histochem Cytochem. 1996 Oct;44(10):1183–1193. doi: 10.1177/44.10.8813084. [DOI] [PubMed] [Google Scholar]