<scp>OFF</scp> bipolar cell density varies by subtype, eccentricity, and along the dorsal ventral axis in the mouse retina

Camerino, Michael J.; Engerbretson, Ian J; Fife, Parker A.; Reynolds, Nathan; Berria, Mikel H.; Doyle, Jamie R.; Clemons, Mellisa R.; Gencarella, Michael D.; Borghuis, Bart G.; Fuerst, Peter G.

doi:10.1002/cne.25064

Cited by 12 publications

(15 citation statements)

References 63 publications

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“…Traditional immunofluorescence (IF) was performed to label RBCs, cone bipolar cells (CBCs), and M€ uller glia in age-matched mice and showed that cells classified by IF or SABER-FISH had nearly identical locations (Figure S2H). The average density of classified bipolar cells was 40,592 ± 5,806 bipolar cells/mm 2 (mean ± SD across retinas), which agrees with the previous estimate of 39,975 ± 6,339 bipolar cells/mm 2 based on a combination of transgenic mouse lines and type-specific antibodies (Figure S2I) (Camerino et al, 2021;Nadal-Nicola ´s et al, 2020;Wassle et al, 2009). These data validate the use of combinatorial SABER-FISH to classify cell populations.…”

Section: Capturing the Complete Diversity Of Bipolar Subtypes In Situsupporting

confidence: 89%

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity

et al. 2022

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How do neuronal subtypes emerge during development? Recent molecular studies have profiled existing neuronal diversity, but neuronal subtype genesis remains elusive. The 15 types of mouse retinal bipolar interneurons are characterized by distinct functions, morphologies, and transcriptional profiles. Here, we develop a comprehensive spatiotemporal map of bipolar subtype genesis in the murine retina. Combining multiplexed detection of 16 RNA markers with timed delivery of 5-ethynyl uridine (EdU) and bromodeoxyuridine (BrdU), we analyze more than 30,000 single cells in full retinal sections to classify all bipolar subtypes and their birthdates. We find that bipolar subtype birthdates are ordered and follow a centrifugal developmental axis. Spatial analysis reveals a striking wave pattern of bipolar subtype birthdates, and lineage analyses suggest clonal restriction on homotypic subtype production. These results inspire a hierarchical developmental model, with ordered subtype genesis within lineages. Our results provide insight into neuronal subtype development and establish a framework for studying subtype diversification.

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Section: Capturing the Complete Diversity Of Bipolar Subtypes In Situsupporting

confidence: 89%

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity

et al. 2022

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“…Slightly higher density of OFF subtypes were observed in the ventral retina compared to the dorsal retina, consistent with previous analyses (Supplementary Fig 1I) [9]. Similarly, slightly higher ventral density of Type 9 was observed, consistent with a recent observation of ventral enrichment for this S-cone selective subtype (Supplementary Fig.…”

Section: Resultssupporting

confidence: 91%

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity

West

Lapan

Lee

et al. 2021

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How do neuronal subtypes emerge during development? Recent molecular studies have expanded our knowledge of existing neuronal diversity. However, the genesis of neuronal subtypes remains elusive and previous studies have been limited by a lack of quantitative methods for simultaneous detection of subtype diversity in situ. The bipolar interneurons of the mammalian retina represent a diverse neuronal class, characterized by distinct functions, morphologies, and recently discovered transcriptional profiles. Here, we developed a comprehensive spatiotemporal map of bipolar subtype genesis in the retina. Combining multiplexed detection of 16 RNA markers with timed delivery of EdU and BrdU, we analyzed more than 30,000 single cells in full retinal sections to classify all bipolar subtypes and their birthdates. We found that bipolar subtype birthdates are ordered and follow a centrifugal developmental axis. Spatial analysis revealed a striking oscillatory wave pattern of bipolar subtype birthdates, and lineage analyses suggest clonal restriction on homotypic subtype production. These results inspired a hierarchical model of neuronal subtype genesis in the mammalian retina, with the wave pattern of subtype birthdates arising from early asymmetric cell divisions among founding retinal progenitor cells. Our results provide an outline of the developmental logic that generates diverse neuronal subtypes, and establishes a framework for studying subtype diversification.

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“…Asymmetric distribution of OFF bipolar cells in the retina has been shown by Camerino et al (2021) . They reported that five types of bipolar cells occurred at a higher density in the ventral retina than in the dorsal retina.…”

Section: Resultsmentioning

confidence: 95%

“…Type-dependent, diverse functional architecture is suggested for achromatic cells, such as motion detection ( Euler et al, 2014 ; Hellmer et al, 2021 ). Bipolar cell topography was investigated by Camerino et al (2021) , which revealed that many types of OFF bipolar cells occurred at a higher density in the ventral retina than in the dorsal retina. However, the topography of other types of bipolar cells has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Distributions of Achromatic Bipolar Cells in the Mouse Retina

2022

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In the retina, evolutionary changes can be traced in the topography of photoreceptors. The shape of the visual streak depends on the height of the animal and its habitat, namely, woods, prairies, or mountains. Also, the distribution of distinct wavelength-sensitive cones is unique to each animal. For example, UV and green cones reside in the ventral and dorsal regions in the mouse retina, respectively, whereas in the rat retina these cones are homogeneously distributed. In contrast with the abundant investigation on the distribution of photoreceptors and the third-order neurons, the distribution of bipolar cells has not been well understood. We utilized two enhanced green fluorescent protein (EGFP) mouse lines, Lhx4-EGFP (Lhx4) and 6030405A18Rik-EGFP (Rik), to examine the topographic distributions of bipolar cells in the retina. First, we characterized their GFP-expressing cells using type-specific markers. We found that GFP was expressed by type 2, type 3a, and type 6 bipolar cells in the Rik mice and by type 3b, type 4, and type 5 bipolar cells in the Lhx4 mice. All these types are achromatic. Then, we examined the distributions of bipolar cells in the four cardinal directions and three different eccentricities of the retinal tissue. In the Rik mice, GFP-expressing bipolar cells were more highly observed in the nasal region than those in the temporal retina. The number of GFP cells was not different along with the ventral-dorsal axis. In contrast, in the Lhx4 mice, GFP-expressing cells occurred at a higher density in the ventral region than in the dorsal retina. However, no difference was observed along the nasal-temporal axis. Furthermore, we examined which type of bipolar cells contributed to the asymmetric distributions in the Rik mice. We found that type 3a bipolar cells occurred at a higher density in the temporal region, whereas type 6 bipolar cells were denser in the nasal region. The asymmetricity of these bipolar cells shaped the uneven distribution of the GFP cells in the Rik mice. In conclusion, we found that a subset of achromatic bipolar cells is asymmetrically distributed in the mouse retina, suggesting their unique roles in achromatic visual processing.

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OFF bipolar cell density varies by subtype, eccentricity, and along the dorsal ventral axis in the mouse retina

Cited by 12 publications

References 63 publications

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity

Asymmetric Distributions of Achromatic Bipolar Cells in the Mouse Retina

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