Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs

被引:439
作者
Yi, R
O'Carroll, D
Pasolli, HA
Zhang, ZH
Dietrich, FS
Tarakhovsky, A
Fuchs, E
机构
[1] Rockefeller Univ, Lab Lymphocyte Signaling, New York, NY 10021 USA
[2] Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10021 USA
[3] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
关键词
D O I
10.1038/ng1744
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
During embryogenesis, multipotent progenitors within the single-layered surface epithelium differentiate to form the epidermis and its appendages. Here, we show that microRNAs (miRNAs) have an essential role in orchestrating these events. We cloned more than 100 miRNAs from skin and show that epidermis and hair follicles differentially express discrete miRNA families. To explore the functional significance of this finding, we conditionally targeted Dicer1 gene ablation in embryonic skin progenitors. Within the first week after loss of miRNA expression, cell fate specification and differentiation were not markedly impaired, and in the interfollicular epidermis, apoptosis was not markedly increased. Notably, however, developing hair germs evaginate rather than invaginate, thereby perturbing the epidermal organization. Here we characterize miRNAs in skin, the existence of which was hitherto unappreciated, and demonstrate their differential expression and importance in the morphogenesis of epithelial tissues within this vital organ.
引用
收藏
页码:356 / 362
页数:7
相关论文
共 29 条
[1]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[2]   Dicer is essential for mouse development [J].
Bernstein, E ;
Kim, SY ;
Carmell, MA ;
Murchison, EP ;
Alcorn, H ;
Li, MZ ;
Mills, AA ;
Elledge, SJ ;
Anderson, KV ;
Hannon, GJ .
NATURE GENETICS, 2003, 35 (03) :215-217
[3]   Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche [J].
Blanpain, C ;
Lowry, WE ;
Geoghegan, A ;
Polak, L ;
Fuchs, E .
CELL, 2004, 118 (05) :635-648
[4]   MicroRNAs modulate hematopoietic lineage differentiation [J].
Chen, CZ ;
Li, L ;
Lodish, HF ;
Bartel, DP .
SCIENCE, 2004, 303 (5654) :83-86
[5]   The developmental miRNA profiles of zebrafish as determined by small RNA cloning [J].
Chen, PY ;
Manninga, H ;
Slanchev, K ;
Chien, MC ;
Russo, JJ ;
Ju, JY ;
Sheridan, R ;
John, B ;
Marks, DS ;
Gaidatzis, D ;
Sander, C ;
Zavolan, M ;
Tuschl, T .
GENES & DEVELOPMENT, 2005, 19 (11) :1288-1293
[6]   T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer [J].
Cobb, BS ;
Nesterova, TB ;
Thompson, E ;
Hertweck, A ;
O'Connor, E ;
Godwin, J ;
Wilson, CB ;
Brockdorff, N ;
Fisher, AG ;
Smale, ST ;
Merkenschlager, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (09) :1367-1373
[7]   beta 4 integrin is required for hemidesmosome formation, cell adhesion and cell survival [J].
Dowling, J ;
Yu, QC ;
Fuchs, E .
JOURNAL OF CELL BIOLOGY, 1996, 134 (02) :559-572
[8]   Base-calling of automated sequencer traces using phred.: I.: Accuracy assessment [J].
Ewing, B ;
Hillier, L ;
Wendl, MC ;
Green, P .
GENOME RESEARCH, 1998, 8 (03) :175-185
[9]   Dicer is essential for formation of the heterochromatin structure in vertebrate cells [J].
Fukagawa, T ;
Nogami, M ;
Yoshikawa, M ;
Ikeno, M ;
Okazaki, T ;
Takami, Y ;
Nakayama, T ;
Oshimura, M .
NATURE CELL BIOLOGY, 2004, 6 (08) :784-791
[10]   The microRNA Registry [J].
Griffiths-Jones, S .
NUCLEIC ACIDS RESEARCH, 2004, 32 :D109-D111