Tbx1 is regulated by tissue-specific forkhead proteins through a common Sonic hedgehog-responsive enhancer

被引:202
作者
Yamagishi, H
Maeda, J
Hu, TH
McAnally, J
Conway, SJ
Kume, T
Meyers, EN
Yamagishi, C
Srivastava, D
机构
[1] Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA
[3] Med Coll Georgia, Inst Mol Med & Genet, Dept Cell Biol & Anat, Augusta, GA 30912 USA
[4] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN 37232 USA
[5] Duke Univ, Dept Pediat, Durham, NC 27710 USA
[6] Duke Univ, Dept Cell Biol, Durham, NC 27710 USA
关键词
Tbx1; Shh; Fox; DiGeorge syndrome;
D O I
10.1101/gad.1048903
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Haploinsufficiency of Tbx1 is likely a major determinant of cardiac and craniofacial birth defects associated with DiGeorge syndrome. Although mice deficient in Tbx1 exhibit pharyngeal and aortic arch defects, the developmental program and mechanisms through which Tbx1 functions are relatively unknown. We identified a single cis-element upstream of Tbx1 that recognized winged helix/forkhead box (Fox)-containing transcription factors and was essential for regulation of Tbx1 transcription in the pharyngeal endoderm and head mesenchyme. The Tbx1 regulatory region was responsive to signaling by Sonic hedgehog (Shh) in vivo. We show that Shh is necessary for aortic arch development, similar to Tbx1, and is also required for expression of Foxa2 and Foxc:2 in the pharyngeal endoderm. and head mesenchyme, respectively. Foxa2, Foxc1, or Foxc2 could bind and activate transcription through the critical cis-element upstream of Tbx1, and Foxc proteins were required, within their expression domains, for Tbx1 transcription in vivo. We propose that Tbx1 is a direct transcriptional target of Fox proteins and that Fox proteins may serve an intermediary role in Shh regulation of Tbx1.
引用
收藏
页码:269 / 281
页数:13
相关论文
共 50 条
[1]  
Abu-Issa R, 2002, DEVELOPMENT, V129, P4613
[2]   HNF-3-BETA IS ESSENTIAL FOR NODE AND NOTOCHORD FORMATION IN MOUSE DEVELOPMENT [J].
ANG, SL ;
ROSSANT, J .
CELL, 1994, 78 (04) :561-574
[3]   AN ANCIENT FAMILY OF EMBRYONICALLY EXPRESSED MOUSE GENES SHARING A CONSERVED PROTEIN MOTIF WITH THE T-LOCUS [J].
BOLLAG, RJ ;
SIEGFRIED, Z ;
CEBRATHOMAS, JA ;
GARVEY, N ;
DAVIDSON, EM ;
SILVER, LM .
NATURE GENETICS, 1994, 7 (03) :383-389
[4]  
Chapman DL, 1996, DEV DYNAM, V206, P379, DOI 10.1002/(SICI)1097-0177(199608)206:4<379::AID-AJA4>3.0.CO
[5]  
2-F
[6]   Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function [J].
Chiang, C ;
Ying, LTT ;
Lee, E ;
Young, KE ;
Corden, JL ;
Westphal, H ;
Beachy, PA .
NATURE, 1996, 383 (6599) :407-413
[7]   Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4 [J].
Cirillo, LA ;
Lin, FR ;
Cuesta, I ;
Friedman, D ;
Jarnik, M ;
Zaret, KS .
MOLECULAR CELL, 2002, 9 (02) :279-289
[8]   Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome [J].
Fang, JM ;
Dagenais, SL ;
Erickson, RP ;
Arlt, MF ;
Glynn, MW ;
Gorski, JL ;
Seaver, LH ;
Glover, TW .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (06) :1382-1388
[9]  
Frank DU, 2002, DEVELOPMENT, V129, P4591
[10]   Tbx1, a DiGeorge syndrome candidate gene, is regulated by Sonic hedgehog during pharyngeal arch development [J].
Garg, V ;
Yamagishi, C ;
Hu, TH ;
Kathiriya, IS ;
Yamagishi, H ;
Srivastava, D .
DEVELOPMENTAL BIOLOGY, 2001, 235 (01) :62-73