Abstract:
:Screens for genes that orchestrate neural circuit formation in mammals have been hindered by practical constraints of germline mutagenesis. To overcome these limitations, we combined RNA-seq with somatic CRISPR mutagenesis to study synapse development in the mouse retina. Here synapses occur between cellular layers, forming two multilayered neuropils. The outer neuropil, the outer plexiform layer (OPL), contains synapses made by rod and cone photoreceptor axons on rod and cone bipolar dendrites, respectively. We used RNA-seq to identify selectively expressed genes encoding cell surface and secreted proteins and CRISPR-Cas9 electroporation with cell-specific promoters to assess their roles in OPL development. Among the genes identified in this way are Wnt5a and Wnt5b. They are produced by rod bipolars and activate a non-canonical signaling pathway in rods to regulate early OPL patterning. The approach we use here can be applied to other parts of the brain.
journal_name
Neuronjournal_title
Neuronauthors
Sarin S,Zuniga-Sanchez E,Kurmangaliyev YZ,Cousins H,Patel M,Hernandez J,Zhang KX,Samuel MA,Morey M,Sanes JR,Zipursky SLdoi
10.1016/j.neuron.2018.03.004subject
Has Abstractpub_date
2018-04-04 00:00:00pages
109-126.e8issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(18)30181-8journal_volume
98pub_type
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