Craniofacial anomalies of the cultured mouse embryo induced by inhibition of sonic hedgehog signaling: An animal model of holoprosencephaly

被引:32
作者
Nagase, T
Nagase, M
Osumi, N
Fukuda, S
Nakamura, S
Ohsaki, K
Harii, K
Asato, H
Yoshimura, K
机构
[1] Univ Tokyo, Grad Sch Med, Dept Plast & Reconstruct Surg, Univ Hosp, Tokyo 1138655, Japan
[2] Univ Tokyo, Grad Sch Med, Dept Nephrol & Endocrinol, Univ Hosp, Tokyo 1138655, Japan
[3] Univ Tokyo, Grad Sch Med, Lab Electron Microscopy, Univ Hosp, Tokyo 1138655, Japan
[4] Tohoku Univ, Grad Sch Med, Dept Dev Neurosci, Sendai, Miyagi 980, Japan
[5] Natl Ctr Neurol & Psychiat, Div Biochem & Cellular Biol, Tokyo, Japan
[6] Kyorin Univ, Dept Plast & Reconstruct Surg, Tokyo, Japan
关键词
holoprosencephaly; mouse embryo; neural crest cells; Sonic hedgehog; whole embryo culture;
D O I
10.1097/00001665-200501000-00016
中图分类号
R61 [外科手术学];
学科分类号
摘要
The pathogenesis of holoprosencephaly is multifactorial, and blockage of Sonic hedgehog signaling is one of the most important causative factors in animal models and human cases. In this study, the authors analyzed facial anomalies of mouse embryos, which were cultured in vitro and exposed to cyclopamine, an alkaloid blocker of Sonic hedgehog signaling. When cultured with cyclopamine for embryonic day 8.5 to 10.5, the whole body size was smaller than normal, and the distance and angle between the nasal placodes were remarkably reduced. Extension of the cranial surface vessels also was noted. No cyclopia was observed. Migration of the cranial neural crest cells seemed to be intact. Expressions of Patched-1 and Gli-1, downstream genes of Sonic hedgehog signaling, also were down-regulated in in situ hybridization and real-time reverse transcriptase-polymerase chain reaction analyses. The authors consider that these facial anomalies represent milder phenotypes of holoprosencephaly.
引用
收藏
页码:80 / 88
页数:9
相关论文
共 38 条
[1]   Inhibition of Sonic hedgehog signaling in vivo results in craniofacial neural crest cell death [J].
Ahlgren, SC ;
Bronner-Fraser, M .
CURRENT BIOLOGY, 1999, 9 (22) :1304-1314
[2]   Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure [J].
Ahlgren, SC ;
Thakur, V ;
Bronner-Fraser, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) :10476-10481
[3]   Mouse GLI3 regulates Fgf8 expression and apoptosis in the developing neural tube, face, and limb bud [J].
Aoto, K ;
Nishimura, T ;
Eto, K ;
Motoyame, J .
DEVELOPMENTAL BIOLOGY, 2002, 251 (02) :320-332
[4]   Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly [J].
Belloni, E ;
Muenke, M ;
Roessler, E ;
Traverso, G ;
SiegelBartelt, J ;
Frumkin, A ;
Mitchell, HF ;
DonisKeller, H ;
Helms, C ;
Hing, AV ;
Heng, HHQ ;
Koop, B ;
Martindale, D ;
Rommens, JM ;
Tsui, LC ;
Scherer, SW .
NATURE GENETICS, 1996, 14 (03) :353-356
[5]   Development of the facial midline [J].
Carstens, MH .
JOURNAL OF CRANIOFACIAL SURGERY, 2002, 13 (01) :129-187
[6]   Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened [J].
Chen, JK ;
Taipale, J ;
Cooper, MK ;
Beachy, PA .
GENES & DEVELOPMENT, 2002, 16 (21) :2743-2748
[7]   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
[8]   Malformations of the craniofacial region: Evolutionary, embryonic, genetic, and clinical perspectives [J].
Cohen, MM .
AMERICAN JOURNAL OF MEDICAL GENETICS, 2002, 115 (04) :245-268
[9]   The Hedgehog signaling network [J].
Cohen, MM .
AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2003, 123A (01) :5-28
[10]   Teratogenesis of holoprosencephaly [J].
Cohen, MM ;
Shiota, K .
AMERICAN JOURNAL OF MEDICAL GENETICS, 2002, 109 (01) :1-15