Abstract：
:The rich functional diversity of the nervous system is founded in the specific connectivity of the underlying neural circuitry. Neurons are often preprogrammed to respond to multiple axon guidance signals because they use sequential guideposts along their pathways, but this necessitates a strict spatiotemporal regulation of intracellular signaling to ensure the cues are detected in the correct order. We performed a mouse mutagenesis screen and identified the Rho GTPase antagonist p190RhoGAP as a critical regulator of motor axon guidance. Rather than acting as a compulsory signal relay, p190RhoGAP uses a non-conventional GAP-independent mode to transiently suppress attraction to Netrin-1 while motor axons exit the spinal cord. Once in the periphery, a subset of axons requires p190RhoGAP-mediated inhibition of Rho signaling to target specific muscles. Thus, the multifunctional activity of p190RhoGAP emerges from its modular design. Our findings reveal a cell-intrinsic gate that filters conflicting signals, establishing temporal windows of signal detection.
journal_name
Neuronjournal_title
Neuronauthors
Bonanomi D,Valenza F,Chivatakarn O,Sternfeld MJ,Driscoll SP,Aslanian A,Lettieri K,Gullo M,Badaloni A,Lewcock JW,Hunter T,Pfaff SLdoi
10.1016/j.neuron.2019.02.034subject
Has Abstractpub_date
2019-05-08 00:00:00pages
602-620.e9issue
3eissn
0896-6273issn
1097-4199pii
S0896-6273(19)30169-2journal_volume
102pub_type
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