Journal article
The Down Syndrome Critical Region Regulates Retinogeniculate Refinement
The Journal of neuroscience, Vol.31(15), pp.5764-5776
04/13/2011
Handle:
https://hdl.handle.net/2376/110433
PMCID: PMC3230532
PMID: 21490218
Abstract
Down syndrome (DS) is a developmental disorder caused by a third chromosome 21 in humans (Trisomy 21), leading to neurological deficits and cognitive impairment. Studies in mouse models of DS suggest that cognitive deficits in the adult are associated with deficits in synaptic learning and memory mechanisms, but it is unclear whether alterations in the early wiring and refinement of neuronal circuits contribute to these deficits. Here, we show that early developmental refinement of visual circuits is perturbed in mouse models of Down syndrome. Specifically, we find excessive eye-specific segregation of retinal axons in the dorsal lateral geniculate nucleus. Indeed, the degree of refinement scales with defects in the “Down syndrome critical region” (DSCR) in a dose-dependent manner. We further identify
Dscam
(Down syndrome cell adhesion molecule), a gene within the DSCR, as a regulator of eye-specific segregation of retinogeniculate projections. Although
Dscam
is not the sole gene in the DSCR contributing to enhanced refinement in trisomy,
Dscam
dosage clearly regulates cell spacing and dendritic fasciculation in a specific class of retinal ganglion cells. Thus, altered developmental refinement of visual circuits that occurs before sensory experience is likely to contribute to visual impairment in individuals with Down syndrome.
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Details
- Title
- The Down Syndrome Critical Region Regulates Retinogeniculate Refinement
- Creators
- Martina Blank - Departments of Psychiatry and Behavioral Sciences andPeter G Fuerst - The Jackson Laboratory, Bar Harbor, Maine 04609Beth Stevens - Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Navid Nouri - Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Lowry Kirkby - Department of Molecular and Cell Biology, University of California, Berkeley, California 94720Deepti Warrier - Departments of Psychiatry and Behavioral Sciences andBen A Barres - Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Marla B Feller - Department of Molecular and Cell Biology, University of California, Berkeley, California 94720Andrew D Huberman - Neurosciences Department in the School of Medicine, and Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093Robert W Burgess - Neurobiology, Stanford University School of Medicine, Stanford, California, 94305Craig C Garner - Departments of Psychiatry and Behavioral Sciences and
- Publication Details
- The Journal of neuroscience, Vol.31(15), pp.5764-5776
- Academic Unit
- Center for Reproductive Biology
- Publisher
- Society for Neuroscience
- Identifiers
- 99900547483801842
- Language
- English
- Resource Type
- Journal article