Dlx5 and Dlx6 homeobox genes are required for specification of the mammalian vestibular apparatus

被引:42
作者
Robledo, Raymond F.
Lufkin, Thomas
机构
[1] Genome Inst Singapore, Singapore 138672, Singapore
[2] Jackson Lab, Bar Harbor, ME USA
关键词
inner ear; mouse mutant; homeobox genes; patterning; otocyst; otic vesicle;
D O I
10.1002/dvg.20233
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mammalian inner ear is a complex organ that develops from a surface ectoderm into distinct auditory and vestibular components. Congenital malformation of these two components resulting from single or multiple gene defects is a common clinical occurrence and is observed in patients with split hand/split foot malformation, a malformation which is phenocopied by D1x516 null mice. Analysis of mice lacking D1x5 and D1x6 homeobox genes identified their restricted and combined expression in the otic epithelium as a crucial regulator of vestibular cell fates. Otic induction initiates without incident in D1x5/6(-/-) embryos, but dorsal otic derivatives including the semicircular ducts, utricle, saccule, and endolymphatic duct fail to form. D1x5 and D1x6 seem to influence vestibular cell fates by restricting Pax2 and activating Gbx2 and Bmp4 expression domains. Given their proximity to the disease locus and the observed phenotype in D1x5/6 null mice, D1x5/6 are likely candidates to mediate the inner ear defects observed in patients with split hand/split foot malformation.
引用
收藏
页码:425 / 437
页数:13
相关论文
共 48 条
  • [1] Acampora D, 1999, DEVELOPMENT, V126, P3795
  • [2] Anagnostopoulos AV, 2002, TRENDS GENET, V18, P499
  • [3] Vertebrate cranial placodes I. Embryonic induction
    Baker, CVH
    Bronner-Fraser, M
    [J]. DEVELOPMENTAL BIOLOGY, 2001, 232 (01) : 1 - 61
  • [4] Role of the hindbrain in dorsoventral but not anteroposterior axial specification of the inner ear
    Bok, JW
    Bronner-Fraser, M
    Wu, DK
    [J]. DEVELOPMENT, 2005, 132 (09): : 2115 - 2124
  • [5] Ectopic Noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear
    Chang, WS
    Nunes, FD
    De Jesus-Escobar, JM
    Harland, R
    Wu, DK
    [J]. DEVELOPMENTAL BIOLOGY, 1999, 216 (01) : 369 - 381
  • [6] Molecular mechanisms underlying inner ear patterning defects in kreisler mutants
    Choo, D
    Ward, J
    Reece, A
    Dou, HW
    Lin, ZS
    Greinwald, J
    [J]. DEVELOPMENTAL BIOLOGY, 2006, 289 (02) : 308 - 317
  • [7] Characterization of the split hand split foot malformation locus SHFM1 at 7q21.3-q22.1 and analysis of a candidate gene for its expression during limb development
    Crackower, MA
    Scherer, SW
    Rommens, JM
    Hui, CC
    Poorkaj, P
    Soder, S
    Cobben, JM
    Hudgins, L
    Evans, JP
    Tsui, LC
    [J]. HUMAN MOLECULAR GENETICS, 1996, 5 (05) : 571 - 579
  • [8] Specification of jaw subdivisions by Dix genes
    Depew, MJ
    Lufkin, T
    Rubenstein, JLR
    [J]. SCIENCE, 2002, 298 (5592) : 381 - 385
  • [9] Depew MJ, 1999, DEVELOPMENT, V126, P3831
  • [10] Dong PDS, 2002, DEVELOPMENT, V129, P1967