Function of Rieger syndrome gene in left-right asymmetry and craniofacial development

被引:410
作者
Lu, MF
Pressman, C
Dyer, R
Johnson, RL
Martin, JF
机构
[1] Texas A&M Univ Syst Hlth Sci Ctr, Ctr Canc Biol & Nutr, Alkek Inst Biosci & Technol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA
关键词
D O I
10.1038/45797
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
Rieger syndrome, an autosomal dominant disorder, includes ocular, craniofacial and umbilical abnormalities, The pitx2 homeobox gene, which is mutated in Rieger syndrome(1,2), has been proposed to be the effector molecule interpreting left-right axial information from the early embryonic trunk to each organ(3-7). Here we have used gene targeting in mice to generate a loss-of-function allele that would be predicted to result in organ randomization or isomerization. Although pitx2(-/-) embryos had abnormal cardiac morphogenesis, mutant hearts looped in the normal direction. Pitx2(-/-) embryos had correctly oriented, but arrested, embryonic rotation and right pulmonary isomerism. They also had defective development of the mandibular and maxillary facial prominences, regression of the stomodeum and arrested tooth development. Fgf8 expression was absent, and Bmp4 expression was expanded in the branchial-arch ectoderm. These data reveal a critical role for pitx2 in left-right asymmetry but indicate that pitx2 may function at an intermediate step in cardiac morphogenesis and embryonic rotation.
引用
收藏
页码:276 / 278
页数:3
相关论文
共 20 条
  • [1] Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development
    Biben, C
    Harvey, RP
    [J]. GENES & DEVELOPMENT, 1997, 11 (11) : 1357 - 1369
  • [2] Campione M, 1999, DEVELOPMENT, V126, P1225
  • [3] Construction and analysis of a sequence-ready map in 4q25:: Rieger syndrome can be caused by haploinsufficiency of RIEG, but also by chromosome breaks ≈90 kb upstream of this gene
    Flomen, RH
    Vatcheva, R
    Gorman, PA
    Baptista, PR
    Groet, J
    Barisic, I
    Ligutic, I
    Nizetic, D
    [J]. GENOMICS, 1998, 47 (03) : 409 - 413
  • [4] Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation
    Gage, PJ
    Camper, SA
    [J]. HUMAN MOLECULAR GENETICS, 1997, 6 (03) : 457 - 464
  • [5] X-linked situs abnormalities result from mutations in ZIC3
    Gebbia, M
    Ferrero, GB
    Pilia, G
    Bassi, MT
    Aylsworth, AS
    PenmanSplitt, M
    Bird, LM
    Bamforth, JS
    Burn, J
    Schlessinger, D
    Nelson, DL
    Casey, B
    [J]. NATURE GENETICS, 1997, 17 (03) : 305 - 308
  • [6] Links in the left/right axial pathway
    Harvey, RP
    [J]. CELL, 1998, 94 (03) : 273 - 276
  • [7] JOHNSTON MC, 1979, EXP EYE RES, V29, P27, DOI 10.1016/0014-4835(79)90164-7
  • [8] Kaufman M. H., 1992, ATLAS MOUSE DEV
  • [9] The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals
    Logan, M
    Pagán-Westphal, SM
    Smith, DM
    Paganessi, L
    Tabin, CJ
    [J]. CELL, 1998, 94 (03) : 307 - 317
  • [10] Lu MF, 1999, DEVELOPMENT, V126, P495