γ-Protocadherins regulate neuronal survival but are dispensable for circuit formation in retina
Abstract
Twenty-two tandemly arranged protocadherin-γ (Pcdh-γ) genes encode transmembrane proteins with distinct cadherin-related extracellular domains and a common intracellular domain. Genetic studies have implicated Pcdh-γ genes in the regulation of neuronal survival and synapse formation. Because mice lacking the Pcdh-γ cluster die perinatally, we generated conditional mutants to analyze roles of Pcdh-γ genes in the development and function of neural circuits. Retina-specific deletion of Pcdh-γs led to accentuation of naturally occurring death of interneurons and retinal ganglion cells (RGCs) during the first two postnatal weeks. Nonetheless, many neuronal subtypes formed lamina-specific arbors. Blocking apoptosis by deletion of the pro-apoptotic gene Bax showed that even neurons destined to die formed qualitatively and quantitatively appropriate connections. Moreover, electrophysiological analysis indicated that processing of visual information was largely normal in the absence of Pcdh-γ genes. These results suggest that Pcdh-γ genes are dispensable for elaboration of specific connections in retina, but play a primary role in sculpting neuronal populations to appropriate sizes or proportions during the period of naturally occurring cell death.
Additional Information
© 2008 Company of Biologists. Accepted September 24, 2008. We thank Joshua Weiner for sharing data. This work was supported by grants from the National Institutes of Health to M.M. and J.R.S, a NARSAD Young Investigator award to J.L., and Damon Runyon Cancer Research Foundation Fellowship to Y.-F.Z.Attached Files
Published - 4141.full.pdf
Supplemental Material - 027912-figS1.pdf
Supplemental Material - 027912-figS2.pdf
Supplemental Material - 027912-figS3.pdf
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Additional details
- Alternative title
- Gamma Protocadherins regulate neuronal survival but are dispensable for circuit formation in retina
- PMCID
- PMC2644426
- Eprint ID
- 75702
- DOI
- 10.1242/dev.027912
- Resolver ID
- CaltechAUTHORS:20170404-141850023
- NIH
- Brain and Behavior Research Foundation
- Damon Runyon Cancer Research Foundation
- Created
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2017-04-04Created from EPrint's datestamp field
- Updated
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2021-11-15Created from EPrint's last_modified field