Retina development in zebrafish requires the heparan sulfate proteoglycan agrin

被引:24
作者
Liu, I-Hsuan [1 ]
Zhang, Chengjin [1 ]
Kim, Min Jung [2 ]
Cole, Gregory J. [1 ,3 ]
机构
[1] Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA
[2] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA
[3] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA
关键词
agrin; Fgf; zebrafish; retinotectal; Pax; 6; heparan sulfate proteoglycan;
D O I
10.1002/dneu.20625
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Recent studies from our laboratory have begun to elucidate the role of agrin in zebrafish development. One agrin morphant phenotype that results from agrin knockdown is microphthalmia (reduced eye size). To begin to understand the mechanisms underlying the role of agrin in eye development, we have analyzed retina development in agrin morphants. Retinal differentiation is impaired in agrin morphants, with retinal lamination being disrupted following agrin morpholino treatment. Pax 6.1 and Mbx1 gene expression, markers of eye development, are markedly reduced in agrin morphants. Formation of the optic fiber layer of the zebrafish retina is also impaired, exhibited as both reduced size of the optic fiber layer, and disruption of retinal ganglion cell axon growth to the optic tectum. The retinotectal topographic projection to the optic tectum is perturbed in agrin morphants in association with a marked loss of heparan sulfate expression in the retinotectal pathway, with this phenotype resembling retinotectal phenotypes observed in mutant zebrafish lacking enzymes for heparan sulfate synthesis. Treatment of agrin morphants with a fibroblast growth factor (Fgf) receptor inhibitor, rescue of the retinal lamination phenotype by transplantation of Fgf8-coated beads, and disruption of both the expression of Fgf-dependent genes and activation of ERK in agrin morphants provides evidence that agrin modulation of Fgf function contributes to retina development. Collectively, these agrin morphant phenotypes provide support for a crucial role of agrin in retina development and formation of an ordered retinotectal topographic map in the optic tectum of zebrafish. (C) 2008 Wiley Periodicals, Inc.
引用
收藏
页码:877 / 898
页数:22
相关论文
共 99 条
  • [21] Fashena D, 1999, J COMP NEUROL, V406, P415, DOI 10.1002/(SICI)1096-9861(19990412)406:3<415::AID-CNE9>3.0.CO
  • [22] 2-2
  • [23] Defects in eye development in transgenic mice overexpressing the heparan sulfate proteoglycan agrin
    Fuerst, Peter G.
    Rauch, Steven M.
    Burgess, Robert W.
    [J]. DEVELOPMENTAL BIOLOGY, 2007, 303 (01) : 165 - 180
  • [24] Daily regulates Dpp morphogen gradient formation in the Drosophila wing
    Fujise, M
    Takeo, S
    Kamimura, K
    Matsuo, T
    Aigaki, T
    Izumi, S
    Nakato, H
    [J]. DEVELOPMENT, 2003, 130 (08): : 1515 - 1522
  • [25] Defective neuromuscular synaptogenesis in agrin-deficient mutant mice
    Gautam, M
    Noakes, PG
    Moscoso, L
    Rupp, F
    Scheller, RH
    Merlie, JP
    Sanes, JR
    [J]. CELL, 1996, 85 (04) : 525 - 535
  • [26] Agrin plays an organizing role in the formation of sympathetic synapses
    Gingras, J
    Rassadi, S
    Cooper, E
    Ferns, M
    [J]. JOURNAL OF CELL BIOLOGY, 2002, 158 (06) : 1109 - 1118
  • [27] GENOMIC STRUCTURE, EVOLUTIONARY CONSERVATION AND ANIRIDIA MUTATIONS IN THE HUMAN PAX6 GENE
    GLASER, T
    WALTON, DS
    MAAS, RL
    [J]. NATURE GENETICS, 1992, 2 (03) : 232 - 239
  • [28] Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function
    Grobe, K
    Inatani, M
    Pallerla, SR
    Castagnola, J
    Yamaguchi, Y
    Esko, JD
    [J]. DEVELOPMENT, 2005, 132 (16): : 3777 - 3786
  • [29] Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane
    Groffen, AJA
    Veerkamp, JH
    Monnens, LAH
    van den Heuvel, LPWJ
    [J]. NEPHROLOGY DIALYSIS TRANSPLANTATION, 1999, 14 (09) : 2119 - 2129
  • [30] Basement membrane-dependent survival of retinal ganglion cells
    Halfter, W
    Willem, M
    Mayer, U
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2005, 46 (03) : 1000 - 1009