We demonstrate that the cell adhesion molecule Fasciclin III (FAS3) mediates synaptic target recognition through homophilic interaction. FAS3 is expressed by the RP3 motoneuron and its target muscles during synaptic target recognition. The RP3 growth cone can form synapses on muscles that ectopically express FAS3. This mistargeting is dependent on FAS3 expression in the motoneurons. In addition, when the FAS3-negative aCC and SNa motoneuron growth cones ectopically express FAS3, they gain the ability to recognize FAS3-expressing muscles as alternative targets. We propose that homophilic synaptic target recognition serves as a basic mechanism of neural network formation.

REFERENCES

REFERENCES
Betz
W. J.
,
Wu
L. G.
(
1995
)
Kinetics of synaptic-vesicle recycling.
Curr. Biol
5
,
1098
1101
Broadie
K.
,
Bate
M.
(
1993
)
Innervation directs receptor synthesis and localization in Drosophila embryo synaptogenesis.
Nature
361
,
350
353
Broadie
K. S.
,
Bate
M.
(
1993
)
Development of the embryonic neuromuscular synapse of Drosophila melanogaster.
J. Neurosci
13
,
144
166
Chiba
A.
,
Hing
H.
,
Cash
S.
,
Keshishian
H.
(
1993
)
Growth cone choices of Drosophila motoneurons in response to muscle fiber mismatch.
J. Neurosci
13
,
714
732
Chiba
A.
,
Keshishian
H.
(
1996
)
Neuronal pathfinding and recognition: roles of cell adhesion molecules.
Dev. Biol
180
,
424
432
Chiba
A.
,
Snow
P.
,
Keshishian
H.
,
Hotta
Y.
(
1995
)
Fasciclin III as a synaptic target recognition molecule in Drosophila.
Nature
374
,
166
168
Desai
C. J.
,
Krueger
N. X.
,
Saito
H.
,
Zinn
K.
(
1997
)
Competition and cooperation among receptor tyrosine phosphotases control motoneuron growth cone guidance in Drosophila.
Development
124
,
1941
1952
Doe
C. Q.
,
Hiromi
Y.
,
Gehring
W. J.
,
Goodman
C. S.
(
1988
)
Expression and function of the segmentation gene fushi tarazu during Drosophila neurogenesis.
Science
239
,
170
175
Elkins
T.
,
Zinn
K.
,
McAllister
L.
,
Hoffmann
F. M.
,
Goodman
C. S.
(
1990
)
Genetic analysis of a Drosophila neural cell adhesion molecule: interaction of fasciclin I and Abelson tyrosine kinase mutations.
Cell
60
,
565
575
Estes
P. S.
,
Roos
J.
,
van der Bliek
A.
,
Kelly
R. B.
,
Krishnan
K. S.
,
Ramaswami
M.
(
1996
)
Traffic of dynamin within individual Drosophila synaptic boutons relative to compartment-specific markers.
J. Neurosci
16
,
5443
5456
Fambrough
D.
,
Goodman
C. S.
(
1996
)
The Drosophilabeaten path gene encoded a novel secreted protein that regulates defasciculation at motor axon choice points.
Cell
87
,
1049
1058
Garrity
P. A.
,
Zipursky
S. L.
(
1995
)
Neuronal target recognition.
Cell
83
,
177
185
Gonzalez-Gaitan
M.
,
Jackle
H.
(
1997
)
Role of Drosophila -adaptin in presynaptic vesicle recycling.
Cell
88
,
767
776
Goodman
C. S.
(
1996
)
Mechanisms and molecules that control growth cone guidance.
Annu. Rev. Neurosci
19
,
341
377
Grenningloh
G.
,
Rehm
E. J.
,
Goodman
C. S.
(
1991
)
Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule.
Cell
67
,
45
57
Hall
S. G.
,
Bieber
A. J.
(
1997
)
Mutations in the Drosophila Neuroglian cell adhesion molecule affect motor neuron pathfinding and peripheral nervous system pattherning.
J. Neurobiol
32
,
325
340
Halpern
M. E.
,
Chiba
A.
,
Johansen
J.
,
Keshishian
H.
(
1991
)
Growth cone behavior underlying the development of stereotypic synaptic connections in Drosophila embryos.
J. Neurosci
11
,
3227
3238
Harris
R.
,
Sabatelli
L. M.
,
Seeger
M. A.
(
1996
)
Guidance cues at the Drosophila CNS midline: identification and characterization of two Drosophila Netrin/Unc-6 homologs.
Neuron
17
,
217
228
Hashimoto
C.
,
Gerttula
S.
,
Anderson
K. V.
(
1991
)
Plasma membrane localization of the Toll protein in the syncytial Drosophila embryo: importance of transmembrane signaling for dorsal-ventral pattern formation.
Development
111
,
1021
1028
Haydon
P. G.
,
Drapeau
P.
(
1995
)
From contact to connection: early events during synaptogenesis.
Trends. Neurosci
18
,
196
201
Igarashi
M.
,
Tagaya
M.
,
Komiya
Y.
(
1997
)
The soluble N-ethylmaleimide-sensitive factor attached protein receptor complex in growth cones: molecular aspects of the axon terminal development.
J. Neurosci
17
,
1460
1470
Keshishian
H.
,
Chiba
A.
,
Chang
T. N.
,
Halfon
M. S.
,
Harkins
E. W.
,
Jarecki
J.
,
Wang
L.
,
Anderson
M.
,
Cash
S.
,
Halpern
M. E.
, et al. 
(
1993
)
Cellular mechanisms governing synaptic development in Drosophila melanogaster.
J. Neurobiol
24
,
757
787
Kopczynski
C. C.
,
Davis
G. W.
,
Goodman
C. S.
(
1996
)
A neural tetraspanin, encoded by late bloomer, that facilitates synapse formation.
Science
271
,
1867
1870
Littleton
J. T.
,
Stern
M.
,
Schulze
K.
,
Perin
M.
,
Bellen
H. J.
(
1993
)
Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release.
Cell
74
,
1125
1134
Matthes
D. J.
,
Sink
H.
,
Kolodkin
A. L.
,
Goodman
C. S.
(
1995
)
Semaphorin II can function as a selective inhibitor of specific synaptic arborizations.
Cell
81
,
631
639
Meadows
L. A.
,
Gell
D.
,
Broadie
K.
,
Gould
A. P.
,
White
R. A.
(
1994
)
The cell adhesion molecule, connection, and the development of the Drosophila neuromuscular system.
J. Cell Sci
107
,
321
328
Mitchell
K. J.
,
Doyle
J. L.
,
Serafin
T.
,
Kennedy
T. E.
,
Tessier-Lavigne
M.
,
Goodman
C. S.
,
Dickson
B. J.
(
1996
)
Genetic analysis of Netrin genes in Drosophila: Netrins guide CNS commissural axons and peripheral motor axons.
Neuron
17
,
203
215
Nose
A.
,
Mahajan
V. B.
,
Goodman
C. S.
(
1992
)
Connectin: a homophilic cell adhesion molecule expressed on a subset of muscles and the motoneurons that innervate them in Drosophila.
Cell
70
,
553
567
Nose
A.
,
Takeichi
M.
,
Goodman
C. S.
(
1994
)
Ectopic expression of Connectin reveals a repulsive function during growth cone guidance and synapse formation.
Neuron
13
,
525
39
Nose
A.
,
Umeda
T.
,
Takeichi
M.
(
1997
)
Neuromuscular target recognition by a homophilic interaction of Connectin cell adhesion molecules in Drosophila.
Development
124
,
1433
1441
Patel
N. H.
,
Snow
P. M.
,
Goodman
C. S.
(
1987
)
Characterization and cloning of fasciclin III: a glycoprotein expressed on a subset of neurons and axon pathways in Drosophila.
Cell
48
,
975
988
Prokop
A.
,
Landgraf
M.
,
Rushton
E.
,
Broadie
K.
,
Bate
M.
(
1996
)
Presynaptic development at the Drosophila neuromuscular junction: assembly and localization of presynaptic active zones.
Neuron
17
,
617
626
Rose
D.
,
Zhu
X.
,
Kose
H.
,
Hoang
B.
,
Cho
J.
,
Chiba
A.
(
1997
)
Toll, a muscle cell surface molecule, locally inhibits synaptic initiation of the RP3 motoneuron growth cone in Drosophila.
Development
124
,
1561
1571
Sink
H.
,
Whitington
P. M.
(
1991
)
Location and connectivity of abdominal motoneurons in the embryo and larva of Drosophila melanogaster.
J. Neurobiol
22
,
298
311
Sink
H.
,
Whitington
P. M.
(
1991
)
Pathfinding in the central nervous system and periphery by identified embryonic Drosophila motor axons.
Development
112
,
307
16
Snow
P. M.
,
Bieber
A. J.
,
Goodman
C. S.
(
1989
)
Fasciclin III: a novel homophilic adhesion molecule in Drosophila.
Cell
59
,
313
323
Sperry
R. W.
(
1963
)
Chemoaffinity in the orderly growth of nerve fiber patterns and connections.
Proc. Natl. Acad. Sci. USA
50
,
703
710
Tessier-Lavigne
M.
,
Goodman
C. S.
(
1996
)
The molecular biology of axon guidance.
Science
274
,
1123
1133
Wassenberg
D. R. d.
,
Kronert
W. A.
,
O'Donnell
P. T.
,
Bernstein
S. I.
(
1987
)
Analysis of the 5end of the Drosophila muscle myosin heavy chain gene. Alternatively spliced transcripts initiate at a single site and intron locations are conserved compared to myosin genes of other organisms.
J. Biol. Chem
262
,
10741
10747
Zoran
M. J.
,
Metts
B. A.
,
Poyer
J. C.
(
1996
)
Specific muscle contacts induce increased transmitter release and neuritic arborization in motoneuronal cultures.
Dev. Biol
179
,
212
222
This content is only available via PDF.