A role for Gbx2 in repression of Otx2 and positioning the mid/hindbrain organizer

被引:244
作者
Millett, S
Campbell, K
Epstein, DJ
Losos, K
Harris, E
Joyner, AL
机构
[1] NYU, Sch Med, Dev Genet Program, New York, NY 10016 USA
[2] NYU, Sch Med, Howard Hughes Med Inst, Skirball Inst Biomol Med, New York, NY 10016 USA
[3] NYU, Sch Med, Dept Cell Biol & Physiol & Neurosci, New York, NY 10016 USA
关键词
D O I
10.1038/43664
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
The mid/hindbrain (MHB) junction can act as an organizer to direct the development of the midbrain and anterior hindbrain(1,2) In mice, Otx2 is expressed in the forebrain and midbrain and Gbx2 is expressed in the anterior hindbrain, with a shared border at the level of the MHB organizer. Here we show that, in Gbx2(-/-) mutants, the earliest phenotype is a posterior expansion of the Otx2 domain during early somite stages. Furthermore, organizer genes are expressed at the shifted Otx2 border, but not in a normal spatial relationship. To test whether Gbx2 is sufficient to position the MHB organizer, we transiently expressed Gbx2 in the caudal Otx2 domain and found that the Otx2 caudal border was indeed shifted rostrally and a normal appearing organizer formed at this new Otx2 border. Transgenic embryos then showed an expanded hindbrain and a reduced midbrain at embryonic day 9.5-10. We propose that formation of a normal MHB organizer depends on a sharp Otx2 caudal border and that Gbx2 is required to position and sharpen this border.
引用
收藏
页码:161 / 164
页数:4
相关论文
共 19 条
  • [1] ACAMPORA D, 1995, DEVELOPMENT, V121, P3279
  • [2] Acampora D, 1997, DEVELOPMENT, V124, P3639
  • [3] Epilepsy and brain abnormalities in mice lacking the Otx1 gene
    Acampora, D
    Mazan, S
    Avantaggiato, V
    Barone, P
    Tuorto, F
    Lallemand, Y
    Brulet, P
    Simeone, A
    [J]. NATURE GENETICS, 1996, 14 (02) : 218 - 222
  • [4] FATE AND POTENTIALITIES OF THE AVIAN MESENCEPHALIC METENCEPHALIC NEUROEPITHELIUM
    ALVARADOMALLART, RM
    [J]. JOURNAL OF NEUROBIOLOGY, 1993, 24 (10): : 1341 - 1355
  • [5] [Anonymous], 1994, MANIPULATING MOUSE E
  • [6] ECHELARD Y, 1994, DEVELOPMENT, V120, P2213
  • [7] FROHMAN MA, 1990, DEVELOPMENT, V110, P589
  • [8] INDUCTION OF ECTOPIC ENGRAILED EXPRESSION AND FATE CHANGE IN AVIAN RHOMBOMERES - INTERSEGMENTAL BOUNDARIES AS BARRIERS
    MARTINEZ, S
    MARIN, F
    NIETO, MA
    PUELLES, L
    [J]. MECHANISMS OF DEVELOPMENT, 1995, 51 (2-3) : 289 - 303
  • [9] MOUSE OTX2 FUNCTIONS IN THE FORMATION AND PATTERNING OF ROSTRAL HEAD
    MATSUO, I
    KURATANI, S
    KIMURA, C
    TAKEDA, N
    AIZAWA, S
    [J]. GENES & DEVELOPMENT, 1995, 9 (21) : 2646 - 2658
  • [10] THE MIDBRAIN HINDBRAIN PHENOTYPE OF WNT-1--WNT-1- MICE RESULTS FROM STEPWISE DELETION OF ENGRAILED-EXPRESSING CELLS BY 9.5 DAYS POSTCOITUM
    MCMAHON, AP
    JOYNER, AL
    BRADLEY, A
    MCMAHON, JA
    [J]. CELL, 1992, 69 (04) : 581 - 595