Direction-selective retinal ganglion cells arise from molecularly specified multipotential progenitors

Huerta, Irina De la; Kim, In-Jung; Voinescu, P. Emanuela; Sanes, Joshua R.

doi:10.1073/pnas.1215806109

Cited by 60 publications

(48 citation statements)

References 47 publications

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“…6 I, J, and N). In contrast, another RGC subtype, the On-Off direction-selective RGCs (dsRGCs), labeled by anti-CART (cocaine-and amphetamineregulated transcript) staining (22), exhibited only a 33% loss, which was similar to the extent of total RGC loss ( Fig. 6 K, L, and O).…”

Section: Resultsmentioning

confidence: 80%

“…Interestingly, the onecut factors seem to promote certain subtypes but repress others. The generation of RGC subtypes has just begun to be studied (22) and the molecular markers for most RGC subtypes remain to be identified; therefore, we do not yet have a full picture of how Oc1 and Oc2 regulate RGC subtype formation. However, the many RGC genes identified in our RNASeq analysis, which are expressed in only subsets of RGCs, provide new opportunities for further studying the mechanisms underlying RGC subtype formation.…”

Section: Potential Mechanisms By Which Oc1 and Oc2 Function In Multiplementioning

confidence: 99%

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Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Sapkota

Chintala

et al. 2014

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

136

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Previously, we have shown that Onecut1 (Oc1) and Onecut2 (Oc2) are expressed in retinal progenitor cells, developing retinal ganglion cells (RGCs), and horizontal cells (HCs). However, in Oc1-null mice, we only observed an 80% reduction in HCs, but no defects in other cell types. We postulated that the lack of defects in other cell types in Oc1-null retinas was a result of redundancy with Oc2. To test this theory, we have generated Oc2-null mice and now show that their retinas also only have defects in HCs, with a 50% reduction in their numbers. However, when both Oc1 and Oc2 are knocked out, the retinas exhibit more profound defects in the development of all early retinal cell types, including completely failed genesis of HCs, compromised generation of cones, reduced production (by 30%) of RGCs, and absence of starburst amacrine cells. Cone subtype diversification and RGC subtype composition also were affected in the double-null retina. Using RNA-Seq expression profiling, we have identified downstream genes of Oc1 and Oc2, which not only confirms the redundancy between the two factors and renders a molecular explanation for the defects in the double-null retinas, but also shows that the onecut factors suppress the production of the late cell type, rods, indicating that the two factors contribute to the competence of retinal progenitor cells for the early retinal cell fates. Our results provide insight into how onecut factors regulate the creation of cellular diversity in the retina and, by extension, in the central nervous system in general.transcription factors | neural development | retinal development | cell fate determination | gene regulation

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Section: Resultsmentioning

confidence: 80%

Section: Potential Mechanisms By Which Oc1 and Oc2 Function In Multiplementioning

confidence: 99%

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Sapkota

Chintala

et al. 2014

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

136

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“…A similar principle operates in the vertebrate retina, where subtypes of RGCs and amacrine cells-identified by their physiological light responses, neurotransmitter phenotypes, or gene expression profiles-have stereotyped dendritic projections to IPL sublayers (Figure 4a) (Famiglietti & Kolb 1976, Siegert et al 2009, Wässle 2004. RGC and amacrine subtype fate choices, including laminar-targeting decisions, are correlated with and likely specified by birthdate (Cherry et al 2009, De la Huerta et al 2012, Osterhout et al 2014, Voinescu et al 2009). A few transcription factors controlling laminar choice have been identified, but none of these alter IPL stratification without changing other aspects of cell fate, such as neurotransmitter type (Cherry et al 2011, Kay et al 2011.…”

Section: Dendrite Targeting Is Determined Geneticallymentioning

confidence: 92%

Development of Dendritic Form and Function

Lefebvre¹,

Sanes

Kay

2015

Annu. Rev. Cell Dev. Biol.

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208

207

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The nervous system is populated by numerous types of neurons, each bearing a dendritic arbor with a characteristic morphology. These type-specific features influence many aspects of a neuron's function, including the number and identity of presynaptic inputs and how inputs are integrated to determine firing properties. Here, we review the mechanisms that regulate the construction of cell type-specific dendrite patterns during development. We focus on four aspects of dendrite patterning that are particularly important in determining the function of the mature neuron: (a) dendrite shape, including branching pattern and geometry of the arbor; (b) dendritic arbor size;

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“…A single progenitor, however, can also produce two distinct neuronal subtypes (14)(15)(16)(17). In some instances, neurons of the same functional subtype may also share a common progenitor (18), but their generation may involve both symmetric and asymmetric divisions (13,19,20). Recent retroviral studies in chick retina revealed the presence of two cell clones comprising the same horizontal cell (HC) type (H1 HC) and larger clones with even numbers of H1 and H3 HCs (11).…”

mentioning

confidence: 99%

Cone photoreceptor types in zebrafish are generated by symmetric terminal divisions of dedicated precursors

Suzuki

Bleckert

Williams

et al. 2013

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

210

283

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Proper functioning of sensory systems requires the generation of appropriate numbers and proportions of neuronal subtypes that encode distinct information. Perception of color relies on signals from multiple cone photoreceptor types. In cone-dominated retinas, each cone expresses a single opsin type with peak sensitivity to UV, long (L) (red), medium (M) (green), or short (S) (blue) wavelengths. The modes of cell division generating distinct cone types are unknown. We report here a mechanism whereby zebrafish cone photoreceptors of the same type are produced by symmetric division of dedicated precursors. Transgenic fish in which the thyroid hormone receptor β2 (trβ2) promoter drives fluorescent protein expression before L-cone precursors themselves are produced permitted tracking of their division in vivo. Every L cone in a local region resulted from the terminal division of an L-cone precursor, suggesting that such divisions contribute significantly to L-cone production. Analysis of the fate of isolated pairs of cones and time-lapse observations suggest that other cone types can also arise by symmetric terminal divisions. Such divisions of dedicated precursors may help to rapidly attain the final numbers and proportions of cone types (L > M, UV > S) in zebrafish larvae. Loss-and gain-of-function experiments show that L-opsin expression requires trβ2 activity before cone differentiation. Ectopic expression of trβ2 after cone differentiation produces cones with mixed opsins. Temporal differences in the onset of trβ2 expression could explain why some species have mixed, and others have pure, cone types.vertebrate cone photoreceptors | cone genesis | zebrafish retina | in vivo time-lapse imaging T he proper functioning of neuronal circuits requires the generation and wiring of a diversity of neuronal cell types. A single neuronal cell class often comprises many subtypes that share similar properties, such as neurotransmitter phenotype, but differ in their precise molecular expression profile, morphology, and physiology (1, 2). How neuronal subtypes that share connectivity with the same populations of postsynaptic cells are produced is not well understood, particularly for vertebrate circuits in vivo. Specifically, are distinct presynaptic partner types of a given postsynaptic cell generated together or produced from separate divisions? When during cell genesis do the presynaptic cell types adopt their respective identities?Cell lineage analyses have demonstrated that many neurogenic divisions are asymmetric, sometimes producing distinct neuronal classes or a neuron together with a nonneuronal cell type (3, 4). Examples of progenitors that give rise to a single neuronal class have also been reported (5-13). A single progenitor, however, can also produce two distinct neuronal subtypes (14-17). In some instances, neurons of the same functional subtype may also share a common progenitor (18), but their generation may involve both symmetric and asymmetric divisions (13,19,20). Recent retroviral studies in chick retina r...

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Direction-selective retinal ganglion cells arise from molecularly specified multipotential progenitors

Cited by 60 publications

References 47 publications

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Development of Dendritic Form and Function

Cone photoreceptor types in zebrafish are generated by symmetric terminal divisions of dedicated precursors

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