June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Cdh13 Regulates Wide-Field Neuron Spine Morphogenesis in the Superior Colliculus
Author Affiliations & Notes
  • Angela Matcham
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
    Neuroscience, University of California San Francisco Graduate Division, San Francisco, California, United States
  • Xin Duan
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Angela Matcham None; Xin Duan None
  • Footnotes
    Support  R01EY030138 and R01NS123912
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 35. doi:
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      Angela Matcham, Xin Duan; Cdh13 Regulates Wide-Field Neuron Spine Morphogenesis in the Superior Colliculus. Invest. Ophthalmol. Vis. Sci. 2023;64(8):35.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinal ganglion cell (RGC) wiring with the superior colliculus (SC) is critical for visual processing. How RGC axons form and maintain synaptic contacts with their correct SC partners remains largely unknown. Expanding on our past work identifying combinatorial Type II Cadherins in wiring intra-retinal circuits, this study identified Cadherin-13 (Cdh13) as a candidate for directing synaptic choice at retinotectal synapses. Based on Cdh13's homophilic interactions and specific expression in the retina and the SC, we hypothesized that Cdh13 could be involved in neuron type-specific retinotectal wiring. This study explores Cdh13's role in this process with a primary focus on the regulation of SC spine morphogenesis.

Methods : In situ hybridization and transgenic neuron labeling led to identifying restricted Cdh13 expression in Wide-Field (WF) neurons in the SC. Dendritic and spine morphologies of genetically labeled Cdh13-expressing WF cells were compared between control and Cdh13 knockouts. AAV-mediated Cdh13 knockdown was conducted in the adult retina and SC, respectively, to test the necessity of Cdh13 in directing retinotectal synapse formation.

Results : The majority of WF neurons (Ntsr1-GN209-Cre mouse line) were found to be Cdh13+ (mean = 91.79%±4.69%, n=322 cells). Likewise, neurons expressing Cdh13 were identified as WF cells with high fidelity in Cdh13-CreER; Thy1-LSL-YFP mice. In this mouse line, the CreER knockin allele replaces the first coding exon, allowing for Cdh13-expressing neuron labeling while homozygotes are cdh13 null mutants. In the null mutant (KO), we observed a significant reduction in WF dendritic mature spine density compared to heterozygous littermates (KO:39.30±5.07 spines/um, n=66 dendrites; Control:98.78±7.04 spines/um, n=102 dendrites p<0.0001), with the greatest reduction in apical regions. AAV-mediated adult Cdh13 knockdown in the SC led to similar mature spine reductions. To test Cdh13’s homophilic role, the same AAV-mediated Cdh13 knockdown was delivered to RGCs. WF mature spine density was reduced when innervated by Cdh13-knockdown RGC terminals (56.64±9.807 spines/mm) compared to naïve WF dendrites (79.42±10.93 spines/um)(p<0.001).

Conclusions : Cdh13 expression in SC WF cells regulates neuron-type specific spine morphogenesis. Cdh13-mediated interactions between presynaptic retinal and postsynaptic SC neurons serve as neuron type-specific mechanisms for neuron morphogenesis.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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