The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila

被引:157
作者
Chen, Brian E. [1 ]
Kondo, Masahiro [1 ]
Garnier, Amélie [1 ]
Watson, Fiona L. [1 ]
Puettmann-Holgado, Roland [1 ]
Lamar, David R. [1 ]
Schmucker, Dietmar [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Neurobiol, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA
关键词
D O I
10.1016/j.cell.2006.03.034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alternative splicing of Dscam generates an enormous molecular diversity with maximally 38,016 different receptors. Whether this large diversity is required in vivo is currently unclear. We examined the role of Dscam in neuron-target recognition of single mechanosensory neurons, which connect with different target cells through multiple axonal branches' Analysis of Dscam null neurons demonstrated an essential role of Dscam for growth and directed extension of axon branches. Expression of randomly chosen single isoforms could not rescue connectivity but did restore basic axonal extension and rudimentary branching. Moreover, two Dscam alleles were generated that each reduced the maximally possible Dscam diversity to 22,176 isoforms. Reduction of Dscam diversity resulted in specific connectivity defects of mechanosensory neurons. Furthermore, the observed allele-specific phenotypes suggest functional differences among isoforms. Our findings provide evidence that a very large number of structurally unique receptor isoforms is required to ensure fidelity and precision of neuronal connectivity.
引用
收藏
页码:607 / 620
页数:14
相关论文
共 39 条
[1]   Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at Purkinje axon initial segment [J].
Ango, F ;
di Cristo, G ;
Higashiyama, H ;
Bennett, V ;
Wu, P ;
Huang, ZJ .
CELL, 2004, 119 (02) :257-272
[2]   Molecules, maps and synapse specificity [J].
Benson, DL ;
Colman, DR ;
Huntley, GW .
NATURE REVIEWS NEUROSCIENCE, 2001, 2 (12) :899-909
[3]   A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to α- and β-neurexins [J].
Boucard, AA ;
Chubykin, AA ;
Comoletti, D ;
Taylor, P ;
Südhof, TC .
NEURON, 2005, 48 (02) :229-236
[4]   Immune signalling in neural development, synaptic plasticity and disease [J].
Boulanger, LM ;
Shatz, CJ .
NATURE REVIEWS NEUROSCIENCE, 2004, 5 (07) :521-531
[5]  
Canal I, 1998, J NEUROSCI, V18, P999
[6]   COMPLEMENTARY GRADIENTS IN EXPRESSION AND BINDING OF ELF-1 AND MEK4 IN DEVELOPMENT OF THE TOPOGRAPHIC RETINOTECTAL PROJECTION MAP [J].
CHENG, HJ ;
NAKAMOTO, M ;
BERGEMANN, AD ;
FLANAGAN, JG .
CELL, 1995, 82 (03) :371-381
[7]   A contextual model for axonal sorting into glomeruli in the mouse olfactory system [J].
Feinstein, P ;
Mombaerts, P .
CELL, 2004, 117 (06) :817-831
[8]   The ephrins and Eph receptors in neural development [J].
Flanagan, JG ;
Vanderhaeghen, P .
ANNUAL REVIEW OF NEUROSCIENCE, 1998, 21 :309-345
[10]   SENSORY NEURONS RECOGNISE DEFINED PATHWAYS IN DROSOPHILA CENTRAL NERVOUS-SYSTEM [J].
GHYSEN, A .
NATURE, 1978, 274 (5674) :869-872