Neuronal clustering and fasciculation phenotype in Dscam‐ and Bax‐deficient mouse retinas

Keeley, Patrick W.; Sliff, Buranee J.; Lee, Sammy; Fuerst, Peter G.; Burgess, Robert W.; Eglen, Stephen J.; Reese, Benjamin E.

doi:10.1002/cne.23089

Cited by 12 publications

(26 citation statements)

References 23 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Examples of cone and rod bipolar cell quantification using these procedures have been described previously (Figs. 2, 7, respectively, in Keeley and Reese, 2010).…”

Section: Animals Lim1mentioning

confidence: 96%

“…A borosilicate glass micropipette with a tip diameter of ϳ0.5 m was backfilled with a solution of the lipophilic dye CM-DiI (V22888; Invitrogen) and fastened to a micromanipulator (Burleigh). Single GFP-positive axon terminals of either rod bipolar cells or type 7 cone bipolar cells were targeted for microinjection, as described previously (Keeley and Reese, 2010). CM-DiI was expelled from the pipette tip using positive current until a bolus of dye was clearly visible at the depth of axon stratification.…”

Section: Animals Lim1mentioning

confidence: 99%

“…For each field, the coefficient of variation (CoV) was determined for both pedicle area and active site area by dividing the SD by the mean. In addition, the centroid of each cone pedicle within a field was determined and the resulting X-Y coordinates were used to define the Voronoi domains associated with each pedicle using a customized spatial statistics program developed in MATLAB (MathWorks), as described previously (Keeley et al, 2012).…”

Section: Animals Lim1mentioning

confidence: 99%

“…3lЈ). To examine the morphology of the dendritic arbors of these sprouted rod bipolar cells in greater detail, single cells were labeled by the local application of DiI to their axonal terminals (Keeley and Reese, 2010). As in control retinas, dendrites of single rod bipolar cells in the Lim1-CKO retina bypassed the PNA-positive pedicles (Fig.…”

Section: Rod Photoreceptor Terminals Retract Into the Onlmentioning

confidence: 99%

See 3 more Smart Citations

Development and Plasticity of Outer Retinal Circuitry Following Genetic Removal of Horizontal Cells

Keeley

Luna

Fariss³

et al. 2013

J. Neurosci.

View full text Add to dashboard Cite

The present study examined the consequences of eliminating horizontal cells from the outer retina during embryogenesis upon the organization and assembly of the outer plexiform layer (OPL). Retinal horizontal cells exhibit a migration defect in Lim1-conditional knock-out (Lim1-CKO) mice and become mispositioned in the inner retina before birth, redirecting their dendrites into the inner plexiform layer. The resultant (mature) OPL, developing in the absence of horizontal cells, shows a retraction of rod spherules into the outer nuclear layer and a sprouting of rod bipolar cell dendrites to reach ectopic ribbon-protein puncta. Cone pedicles and the dendrites of type 7 cone bipolar cells retain their characteristic stratification and colocalization within the collapsed OPL, although both are atrophic and the spatial distribution of the pedicles is disrupted. Developmental analysis of Lim1-CKO retina reveals that components of the rod and cone pathways initially co-assemble within their normal strata in the OPL, indicating that horizontal cells are not required for the correct targeting of photoreceptor terminals or bipolar cell dendrites. As the rod spherules begin to retract during the second postnatal week, rod bipolar cells initially show no signs of ectopic growth, sprouting only subsequently and continuing to do so well after the eighth postnatal week. These results demonstrate the critical yet distinctive roles for horizontal cells on the rod and cone pathways and highlight a unique and as-yet-unrecognized maintenance function of an inhibitory interneuron that is not required for the initial targeting and co-stratification of other components in the circuit.

show abstract

“…Examples of cone and rod bipolar cell quantification using these procedures have been described previously (Figs. 2, 7, respectively, in Keeley and Reese, 2010).…”

Section: Animals Lim1mentioning

confidence: 96%

Section: Animals Lim1mentioning

confidence: 99%

Section: Animals Lim1mentioning

confidence: 99%

Section: Rod Photoreceptor Terminals Retract Into the Onlmentioning

confidence: 99%

See 2 more Smart Citations

Development and Plasticity of Outer Retinal Circuitry Following Genetic Removal of Horizontal Cells

Keeley

Luna

Fariss³

et al. 2013

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Recently, however, the EGF-like transmembrane receptor Megf10, which is expressed in only two neuronal populations of the retina, has been shown to mediate recognition and repulsion between like-type cells (3). In another retinal neuronal population, the anti-and proapoptotic factors Bcl2 and Bax have been shown to modulate programmed cell death, a process that yields increased regularity of this mosaic (4,5). Aside from these examples, relatively little is known about the genetic determinants that coordinate these retinal cell biological processes.…”

mentioning

confidence: 99%

Pituitary tumor-transforming gene 1 regulates the patterning of retinal mosaics

Keeley

Zhou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Neurons are commonly organized as regular arrays within a structure, and their patterning is achieved by minimizing the proximity between like-type cells, but molecular mechanisms regulating this process have, until recently, been unexplored. We performed a forward genetic screen using recombinant inbred (RI) strains derived from two parental A/J and C57BL/6J mouse strains to identify genomic loci controlling spacing of cholinergic amacrine cells, which is a subclass of retinal interneuron. We found conspicuous variation in mosaic regularity across these strains and mapped a sizeable proportion of that variation to a locus on chromosome 11 that was subsequently validated with a chromosome substitution strain. Using a bioinformatics approach to narrow the list of potential candidate genes, we identified pituitary tumortransforming gene 1 (Pttg1) as the most promising. Expression of Pttg1 was significantly different between the two parental strains and correlated with mosaic regularity across the RI strains. We identified a seven-nucleotide deletion in the Pttg1 promoter in the C57BL/6J mouse strain and confirmed a direct role for this motif in modulating Pttg1 expression. Analysis of Pttg1 KO mice revealed a reduction in the mosaic regularity of cholinergic amacrine cells, as well as horizontal cells, but not in two other retinal cell types. Together, these results implicate Pttg1 in the regulation of homotypic spacing between specific types of retinal neurons. The genetic variant identified creates a binding motif for the transcriptional activator protein 1 complex, which may be instrumental in driving differential expression of downstream processes that participate in neuronal spacing.L ike many other CNS structures, the retina is composed of recurring modular microcircuits. Distinct neuronal populations are each distributed across the tissue and establish stereotypic patterns of connectivity with one another. To ensure a complete functional coverage by these microcircuits, individual neuronal populations are arranged in regular arrays across the entire retina (1). The regularity of these arrays is achieved by the presence of a zone of exclusion surrounding each cell, minimizing proximity between like-type cells, and although several developmental mechanisms, such as selective cell death and tangential migration, have been shown to mediate formation of such exclusion zones (2), the molecular underpinnings of these processes have received little attention. Recently, however, the EGF-like transmembrane receptor Megf10, which is expressed in only two neuronal populations of the retina, has been shown to mediate recognition and repulsion between like-type cells (3). In another retinal neuronal population, the anti-and proapoptotic factors Bcl2 and Bax have been shown to modulate programmed cell death, a process that yields increased regularity of this mosaic (4, 5). Aside from these examples, relatively little is known about the genetic determinants that coordinate these retinal cell biological processes.In the pre...

show abstract

DSCAM localization and function at the mouse cone synapse

Andrade

Long

Fleming

et al. 2014

J of Comparative Neurology

Self Cite

View full text Add to dashboard Cite

The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for regulation of cell number, soma spacing and cell type specific dendrite avoidance in many types of retinal ganglion and amacrine cells. In this study we assay the organization of cells making up the outer plexiform layer of the retina in the absence of Dscam. Some types of OFF bipolar cells, type 3b and type 4 bipolar cells, had defects in dendrite arborization in the Dscam mutant retina, while other cell types appeared similar to wild type. The cone synapses that these cells project their dendrites to were intact, as visualized by electron microscopy, and had a distribution and density that was not significantly different than wild type. The spacing of type 3b bipolar cell dendrites was further analyzed by Voronoi domain analysis, Density Recovery Profiling (DRP) analysis and Nearest Neighbor Analysis (NNA). Spacing was found to be significantly different when comparing wild type and mutant type 3b bipolar cell dendrites. Defects in arborization of these bipolar cells could not be attributed to the disorganization of inner plexiform layer cells that occurs in the Dscam mutant retina or an increase in cell number, as they arborized when Dscam was targeted in retinal ganglion cells only or in the bax null retina. Localization of DSCAM was assayed and the protein was localized near to cone synapses in mouse, macaque and ground squirrel retinas. DSCAM protein was detected in several types of bipolar cells, including type 3b and type 4 bipolar cells.

show abstract

Neuronal clustering and fasciculation phenotype in Dscam‐ and Bax‐deficient mouse retinas

Cited by 12 publications

References 23 publications

Development and Plasticity of Outer Retinal Circuitry Following Genetic Removal of Horizontal Cells

Development and Plasticity of Outer Retinal Circuitry Following Genetic Removal of Horizontal Cells

Pituitary tumor-transforming gene 1 regulates the patterning of retinal mosaics

DSCAM localization and function at the mouse cone synapse

Contact Info

Product

Resources

About