Conditional activation of Pax6 in the developing cortex of transgenic mice causes progenitor apoptosis

被引:49
作者
Berger, Joachim
Berger, Silke
Tuoc, Tran Cong
D'Amelio, Marcello
Cecconi, Francesco
Gorski, Jessica A.
Jones, Kevin R.
Gruss, Peter
Stoykova, Anastassia [1 ]
机构
[1] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany
[2] DFG, Ctr Mol Physiol Brain, Gottingen, Germany
[3] IRCCS, Fdn Santa Lucia, Dulbecco Telethon Inst, Rome, Italy
[4] Univ Colorado, Boulder, CO 80309 USA
来源
DEVELOPMENT | 2007年 / 134卷 / 07期
关键词
corticogenesis; Cre/loxP; overexpression; Pax6; Pax6-5a; progenitor; apoptosis; mouse;
D O I
10.1242/dev.02809
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
During development, Pax6 is expressed in a rostrolateral-high to caudomedial-low gradient in the majority of the cortical radial glial progenitors and endows them with neurogenic properties. Using a Cre/loxP-based approach, we studied the effect of conditional activation of two Pax6 isoforms, Pax6 and Pax6-5a, on the corticogenesis of transgenic mice. We found that activation of either Pax6 or Pax6-5a inhibits progenitor proliferation in the developing cortex. Upon activation of transgenic Pax6, specific progenitor pools with distinct endogenous Pax6 expression levels at different developmental stages show defects in cell cycle progression and in the acquisition of apoptotic or neuronal cell fate. The results provide new evidence for the complex role of Pax6 in mammalian corticogenesis.
引用
收藏
页码:1311 / 1322
页数:12
相关论文
共 69 条
[1]  
Andrews GL, 2003, J NEUROSCI, V23, P9873
[2]   Role of Fabp7, a downstream gene of Pax6, in the maintenance of neuroepithelial cells during early embryonic development of the rat cortex [J].
Arai, Y ;
Funatsu, N ;
Numayama-Tsuruta, K ;
Nomura, T ;
Nakamura, S ;
Osumi, N .
JOURNAL OF NEUROSCIENCE, 2005, 25 (42) :9752-9761
[3]   Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye [J].
Ashery-Padan, R ;
Marquardt, T ;
Zhou, XL ;
Gruss, P .
GENES & DEVELOPMENT, 2000, 14 (21) :2701-2711
[4]   E1-Ngn2/Cre is a new line for regional activation of cre recombinase in the developing CNS [J].
Berger, J ;
Eckert, S ;
Scardigli, R ;
Guillemot, F ;
Gruss, P ;
Stoykova, A .
GENESIS, 2004, 40 (04) :195-199
[5]   STRUCTURE AND EXPRESSION OF THE MURINE RETINOBLASTOMA GENE AND CHARACTERIZATION OF ITS ENCODED PROTEIN [J].
BERNARDS, R ;
SCHACKLEFORD, GM ;
GERBER, MR ;
HOROWITZ, JM ;
FRIEND, SH ;
SCHARTL, M ;
BOGENMANN, E ;
RAPAPORT, JM ;
MCGEE, T ;
DRYJA, TP ;
WEINBERG, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (17) :6474-6478
[6]   Regulation of area identity in the mammalian neocortex by Emx2 and Pax6 [J].
Bishop, KM ;
Goudreau, G ;
O'Leary, DDM .
SCIENCE, 2000, 288 (5464) :344-349
[7]  
Caric D, 1997, DEVELOPMENT, V124, P5087
[8]   Pax6-induced alteration of cell fate: Shape changes, expression of neuronal a tubulin, postmitotic phenotype, and cell migration [J].
Cartier, L ;
Laforge, T ;
Feki, A ;
Arnaudeau, S ;
Dubois-Dauphin, M ;
Krause, KH .
JOURNAL OF NEUROBIOLOGY, 2006, 66 (05) :421-436
[9]   Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens [J].
Cvekl, A ;
Yang, Y ;
Chauhan, BK ;
Cveklova, K .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2004, 48 (8-9) :829-844
[10]   DNA-SEQUENCE RECOGNITION BY PAX PROTEINS - BIPARTITE STRUCTURE OF THE PAIRED DOMAIN AND ITS BINDING-SITE [J].
CZERNY, T ;
SCHAFFNER, G ;
BUSSLINGER, M .
GENES & DEVELOPMENT, 1993, 7 (10) :2048-2061