RT Journal Article
SR Electronic
T1 <em>Caenorhabditis elegans</em> Flamingo Cadherin <em>fmi-1</em> Regulates GABAergic Neuronal Development
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4196
OP 4211
DO 10.1523/JNEUROSCI.3094-11.2012
VO 32
IS 12
A1 Najarro, Elvis Huarcaya
A1 Wong, Lianna
A1 Zhen, Mei
A1 Carpio, Edgar Pinedo
A1 Goncharov, Alexandr
A1 Garriga, Gian
A1 Lundquist, Erik A.
A1 Jin, Yishi
A1 Ackley, Brian D.
YR 2012
UL http://www.jneurosci.org/content/32/12/4196.abstract
AB In a genetic screen for regulators of synaptic morphology, we identified the single Caenorhabditis elegans flamingo-like cadherin fmi-1. The fmi-1 mutants exhibit defective axon pathfinding, reduced synapse number, aberrant synapse size and morphology, as well as an abnormal accumulation of synaptic vesicles at nonsynaptic regions. Although FMI-1 is primarily expressed in the nervous system, it is not expressed in the ventral D-type (VD) GABAergic motorneurons, which are defective in fmi-1 mutants. The axon and synaptic defects of VD neurons could be rescued when fmi-1 was expressed exclusively in non-VD neighboring neurons, suggesting a cell nonautonomous action of FMI-1. FMI-1 protein that lacked its intracellular domain still retained its ability to rescue the vesicle accumulation defects of GABAergic motorneurons, indicating that the extracellular domain was sufficient for this function of FMI-1 in GABAergic neuromuscular junction development. Mutations in cdh-4, a Fat-like cadherin, cause similar defects in GABAergic motorneurons. The cdh-4 is expressed by the VD neurons and seems to function in the same genetic pathway as fmi-1 to regulate GABAergic neuron development. Thus, fmi-1 and cdh-4 cadherins might act together to regulate synapse development and axon pathfinding.