Inhibition of NF-κB activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis

被引:152
作者
Bushdid, PB
Brantley, DM
Yull, FE
Blaeuer, GL
Hoffman, LH
Niswander, L
Kerr, LD [1 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Vanderbilt Canc Ctr, Nashville, TN 37232 USA
[4] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA
关键词
D O I
10.1038/33435
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In Drosophila, the Dorsal protein establishes the embryonic dorso-ventral axis during development(1), Here we show that the vertebrate homologue of Dorsal, nuclear factor-kappa B (NF-kappa B), is vital for the formation of the proximo-distal organizer of the developing limb bud, the apical ectodermal ridge (AER). Transcription of the NF-kappa B proto-oncogene c-rel is regulated, in part, during morphogenesis of the limb bud by AER-derived signals such as fibroblast growth factors. Interruption of NF-kappa B activity using viral-mediated delivery of an inhibitor results in a highly dysmorphic AER, reduction in overall limb size, loss of distal elements and reversal in the direction of limb outgrowth. Furthermore, inhibition of NF-kappa B activity in limb mesenchyme leads to a reduction in expression of Sonic hedgehog and Twist but derepresses expression of the bone morphogenetic protein-4 gene. These results are the first evidence that vertebrate NF-kappa B proteins act to transmit growth factor signals between the ectoderm and the underlying mesenchyme during embryonic limb formation.
引用
收藏
页码:615 / 618
页数:4
相关论文
共 29 条
[1]  
BECKER TC, 1994, METHOD CELL BIOL, V43, P161
[2]  
BROCKMAN JA, 1995, MOL CELL BIOL, V15, P2809
[3]   Roles for FGF8 in the induction, initiation, and maintenance of chick limb development [J].
Crossley, PH ;
Minowada, G ;
MacArthur, CA ;
Martin, GR .
CELL, 1996, 84 (01) :127-136
[4]   Overexpression of BMP-2 and BMP-4 alters the size and shape of developing skeletal elements in the chick limb [J].
Duprez, D ;
Bella, EJD ;
Richardson, MK ;
Archer, CW ;
Wolpert, L ;
Brickell, PM ;
FrancisWest, PH .
MECHANISMS OF DEVELOPMENT, 1996, 57 (02) :145-157
[5]   SONIC-HEDGEHOG, A MEMBER OF A FAMILY OF PUTATIVE SIGNALING MOLECULES, IS IMPLICATED IN THE REGULATION OF CNS POLARITY [J].
ECHELARD, Y ;
EPSTEIN, DJ ;
STJACQUES, B ;
SHEN, L ;
MOHLER, J ;
MCMAHON, JA ;
MCMAHON, AP .
CELL, 1993, 75 (07) :1417-1430
[6]   FGF-2 - APICAL ECTODERMAL RIDGE GROWTH SIGNAL FOR CHICK LIMB DEVELOPMENT [J].
FALLON, JF ;
LOPEZ, A ;
ROS, MA ;
SAVAGE, MP ;
OLWIN, BB ;
SIMANDL, BK .
SCIENCE, 1994, 264 (5155) :104-107
[7]   Twist protein in mouse embryogenesis [J].
Gitelman, I .
DEVELOPMENTAL BIOLOGY, 1997, 189 (02) :205-214
[8]  
GRUMONT RJ, 1993, CELL GROWTH DIFFER, V4, P731
[9]   A SERIES OF NORMAL STAGES IN THE DEVELOPMENT OF THE CHICK EMBRYO [J].
HAMBURGER, V ;
HAMILTON, HL .
JOURNAL OF MORPHOLOGY, 1951, 88 (01) :49-&
[10]   THE INTERPLAY BETWEEN MULTIPLE ENHANCER AND SILENCER ELEMENTS DEFINES THE PATTERN OF DECAPENTAPLEGIC EXPRESSION [J].
HUANG, JD ;
SCHWYTER, DH ;
SHIROKAWA, JM ;
COUREY, AJ .
GENES & DEVELOPMENT, 1993, 7 (04) :694-704