Dystroglycan is involved in skin morphogenesis downstream of the Notch signaling pathway

被引:24
作者
Sirour, Cathy [1 ]
Hidalgo, Magdalena [1 ,2 ]
Bello, Valerie [1 ]
Buisson, Nicolas [1 ]
Darribere, Thierry [1 ]
Moreau, Nicole [1 ]
机构
[1] Univ Sorbonne, Univ Paris 06, CNRS, Dev Biol Lab,UMR 7622, F-75252 Paris 05, France
[2] Univ Paris 13, Lab Reponses Cellulaires & Fonct Hypoxie, EA2363, F-93017 Bobigny, France
关键词
XENOPUS-LAEVIS; EPITHELIAL DEVELOPMENT; PRIMARY NEUROGENESIS; MUSCULAR-DYSTROPHY; CILIATED CELLS; LAMININ; EMBRYOS; P63; ORGANIZATION; EXPRESSION;
D O I
10.1091/mbc.E11-01-0074
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Dystroglycan (Dg) is a transmembrane protein involved both in the assembly and maintenance of basement membrane structures essential for tissue morphogenesis, and the transmission of signals across the plasma membrane. We used a morpholino knockdown approach to investigate the function of Dg during Xenopus laevis skin morphogenesis. The loss of Dg disrupts epidermal differentiation by affecting the intercalation of multiciliated cells, deposition of laminin, and organization of fibronectin in the extracellular matrix (ECM). Depletion of Dg also affects cell-cell adhesion, as shown by the reduction of E-cadherin expression at the intercellular contacts, without affecting the distribution of beta(1) integrins. This was associated with a decrease of cell proliferation, a disruption of multiciliated-cell intercalation, and the down-regulation of the transcription factor P63, a marker of differentiated epidermis. In addition, we demonstrated that inhibition or activation of the Notch pathway prevents and promotes transcription of X-dg. Our study showed for the first time in vivo that Dg, in addition to organizing laminin in the ECM, also acts as a key signaling component in the Notch pathway.
引用
收藏
页码:2957 / 2969
页数:13
相关论文
共 50 条
[1]   Zebrafish ΔNp63 is a direct target of bmp signaling and encodes a transcriptional repressor blocking neural specification in the ventral ectoderm [J].
Bakkers, J ;
Hild, M ;
Kramer, C ;
Furutani-Seiki, M ;
Hammerschmidt, M .
DEVELOPMENTAL CELL, 2002, 2 (05) :617-627
[2]   Dystroglycan: from biosynthesis to pathogenesis of human disease [J].
Barresi, R ;
Campbell, KP .
JOURNAL OF CELL SCIENCE, 2006, 119 (02) :199-207
[3]   ΔNp63 antagonizes p53 to regulate mesoderm induction in Xenopus laevis [J].
Barton, Christopher E. ;
Tahinci, Emilios ;
Barbieri, Christopher E. ;
Johnson, Kimberly N. ;
Hanson, Alison J. ;
Jernigan, Kristin K. ;
Chen, Tony W. ;
Lee, Ethan ;
Pietenpol, Jennifer A. .
DEVELOPMENTAL BIOLOGY, 2009, 329 (01) :130-139
[4]   Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations [J].
Bateman, John F. ;
Boot-Handford, Raymond P. ;
Lamande, Shireen R. .
NATURE REVIEWS GENETICS, 2009, 10 (03) :173-183
[5]   A function for dystroglycan in pronephros development in Xenopus laevis [J].
Bello, Valerie ;
Sirour, Cathy ;
Moreau, Nicole ;
Denker, Elsa ;
Darribere, Thierry .
DEVELOPMENTAL BIOLOGY, 2008, 317 (01) :106-120
[6]  
BILLETT FS, 1971, J ANAT, V108, P465
[7]   Functional diversity of dystroglycan [J].
Bozzi, Manuela ;
Morlacchi, Simona ;
Bigotti, Maria Giulia ;
Sciandra, Francesca ;
Brancaccio, Andrea .
MATRIX BIOLOGY, 2009, 28 (04) :179-187
[8]   PRIMARY NEUROGENESIS IN XENOPUS EMBRYOS REGULATED BY A HOMOLOG OF THE DROSOPHILA NEUROGENIC GENE-DELTA [J].
CHITNIS, A ;
HENRIQUE, D ;
LEWIS, J ;
ISHHOROWICZ, D ;
KINTNER, C .
NATURE, 1995, 375 (6534) :761-766
[9]   Chimaeric mice deficient in dystroglycans develop muscular dystrophy and have disrupted myoneural synapses [J].
Côté, PD ;
Moukhles, H ;
Lindenbaum, M ;
Carbonetto, S .
NATURE GENETICS, 1999, 23 (03) :338-342
[10]  
Deblandre GA, 1999, DEVELOPMENT, V126, P4715