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

Neuron | Apr 4, 2018

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.

Pubmed ID: 29576390 RIS Download

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Associated grants

  • Agency: NINDS NIH HHS, Id: T32 NS048004
  • Agency: NEI NIH HHS, Id: K99 EY028200
  • Agency: NINDS NIH HHS, Id: P30 NS062685
  • Agency: Howard Hughes Medical Institute, Id: R21 EY025421
  • Agency: NEI NIH HHS, Id: R37 NS029169
  • Agency: NINDS NIH HHS, Id:

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