Abstract
Presenilin-1 (PS1) is a transmembrane protein and is responsible for the development of early-onset familial Alzheimer’s disease. PS1 is essential for neurogenesis, somitogenesis, angiogenesis and cardiac morphogenesis. We report here that PS1 is involved in the development of skin barrier function. PS1-deficient embryos showed an accelerated acquisition of permeability barrier function at embryonic day 17.5 as manifested by the exclusion of a dye solution. While the expression of β-catenin and epidermal differentiation markers such as keratin 1 and loricrin was not substantially altered, an increased accumulation of E-cadherin was observed immunohistochemically in the mutant skin. These results suggest that PS1 regulates the acquisition of permeability barrier function in the skin.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baki L, Marambaud P, Efthimiopoulos S, Georgakopoulos A, Wen P, Cui W, Shioi J, Koo E, Ozawa M, Friedrich VL Jr, Robakis NK (2001) Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex. Proc Natl Acad Sci USA 98:2381–2386
Bowden PE, Quinlan RA, Breitkreutz D, Fusenig NE (1984) Proteolytic modification of acidic and basic keratins during terminal differentiation of mouse and human epidermis. Eur J Biochem 142:29–36
Cruts M, Van Broeckhoven C (1998) Molecular genetics of Alzheimer’s disease. Ann Med 30:560–565
Cruts M, Van Broeckhoven C (1998) Presenilin mutations in Alzheimer’s disease. Hum Mutat 11:183–190
De Strooper B, Annaert W, Cupers P, Saftig P, Craessaerts K, Mumm JS, Schroeter EH, Schrijvers V, Wolfe MS, Ray WJ, Goate A, Kopan R (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522
Gottardi CJ, Gumbiner BM (2004) Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes. J Cell Biol 167:339–349
Hardman MJ, Sisi P, Banbury DN, Byrne C (1998) Patterned acquisition of skin barrier function during development. Development 125:1541–1552
Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W (2001) Beta-catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105:533–545
Kang DE, Soriano S, Frosch MP, Collins T, Naruse S, Sisodia SS, Leibowitz G, Levine F, Koo EH (1999) Presenilin 1 facilitates the constitutive turnover of beta-catenin: differential activity of Alzheimer’s disease-linked PS1 mutants in the beta-catenin-signaling pathway. J Neurosci 19:4229–4237
Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH (2002) Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis. Cell 110:751–762
Koizumi K, Nakajima M, Yuasa S, Saga Y, Sakai T, Kuriyama T, Shirasawa T, Koseki H (2001) The role of presenilin 1 during somite segmentation. Development 128:1391–1402
Koo EH, Kopan R (2004) Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration. Nat Med S26–S33
Marambaud P, Shioi J, Serban G, Georgakopoulos A, Sarner S, Nagy V, Baki L, Wen P, Efthimiopoulos S, Shao Z, Wisniewski T, Robakis NK (2002) A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. EMBO J 21:1948–1956
Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK (2003) A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114:635–645
Nakajima M, Moriizumi E, Koseki H, Shirasawa T (2004) Presenilin 1 is essential for cardiac morphogenesis. Dev Dyn 230:795–799
Nakajima M, Yuasa S, Ueno M, Takakura N, Koseki H, Shirasawa T (2003) Abnormal blood vessel development in mice lacking presenilin-1. Mech Dev 120:657–667
Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, Tonegawa S (1997) Skeletal and CNS defects in presenilin-1-deficient mice. Cell 89:629–639
Shirayoshi Y, Nose A, Iwasaki K, Takeichi M (1986) N-linked oligosaccharides are not involved in the function of a cell–cell binding glycoprotein E-cadherin. Cell Struct Funct 11:245–252
Tunggal JA, Helfrich I, Schmitz A, Schwarz H, Gunzel D, Fromm M, Kemler R, Krieg T, Niessen CM (2005) E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J 24:1146–1156
Wong PC, Zheng H, Chen H, Becher MW, Sirinathsinghji DJ, Trumbauer ME, Chen HY, Price DL, Van der Ploeg LH, Sisodia SS (1997) Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature 387:288–292
Xia X, Qian S, Soriano S, Wu Y, Fletcher AM, Wang XJ, Koo EH, Wu X, Zheng H (2001) Loss of presenilin 1 is associated with enhanced beta-catenin signaling and skin tumorigenesis. Proc Natl Acad Sci USA 98:10863–10868
Yuasa S, Nakajima M, Aizawa H, Sahara N, Koizumi K, Sakai T, Usami M, Kobayashi S, Kuroyanagi H, Mori H, Koseki H, Shirasawa T (2002) Impaired cell cycle control of neuronal precursor cells in the neocortical primordium of presenilin-1-deficient mice. J Neurosci Res 70:501–513
Zhang Z, Hartmann H, Do VM, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Sommer B, van de Wetering M, Clevers H, Saftig P, De Strooper B, He X, Yankner BA (1998) Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Nature 395:698–702
Acknowledgment
The authors thank Dr M. Takeichi for ECCD2 monoclonal antibody.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nakajima, M., Ogawa, M., Shimoda, Y. et al. Accelerated acquisition of permeability barrier function in the skin of presenilin-1-deficient embryos. Arch Dermatol Res 298, 339–345 (2007). https://doi.org/10.1007/s00403-006-0696-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-006-0696-7