Role for Wnt Signaling in Retinal Neuropil Development: Analysis via RNA-Seq and In Vivo Somatic CRISPR Mutagenesis.

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

Neuron

journal_title

Neuron

authors

Sarin S,Zuniga-Sanchez E,Kurmangaliyev YZ,Cousins H,Patel M,Hernandez J,Zhang KX,Samuel MA,Morey M,Sanes JR,Zipursky SL

doi

10.1016/j.neuron.2018.03.004

subject

Has Abstract

pub_date

2018-04-04 00:00:00

pages

109-126.e8

issue

1

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(18)30181-8

journal_volume

98

pub_type

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