Retinal progenitor cells can produce restricted subsets of horizontal cells

Rompani, Santiago B.; Cepko, Constance L.

doi:10.1073/pnas.0709979104

Cited by 67 publications

(69 citation statements)

References 28 publications

(27 reference statements)

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“…These progenitors differ from previously described restricted retinal progenitors (17,19,39,40), which are biased toward generation of specific cell types; in none of these cases has the range of subtypes present in cloned been analyzed. Although completely consistent with previous results on retinal lineage (1-10), our observations suggest that early retinal progenitors are molecularly heterogeneous and committed to extents that had not been appreciated.…”

Section: Discussionmentioning

confidence: 58%

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

Huerta

Kim

Voinescu

et al. 2012

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

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Single progenitors can give rise to any and all of the main retinal cell types: photoreceptors, interneurons (horizontal, bipolar, and amacrine cells), retinal ganglion cells (RGCs), and glia. Many of these types are divisible into multiple functionally, structurally, and molecularly distinct subtypes (e.g., ∼25 for RGCs). It remains unknown when and how progenitors become committed to generate such subtypes. Here, we determine the origin of RGCs that respond selectively to vertical motion and express cadherin 6 (cdh6). Using Cre recombinase-based lineage tracing, we show that these RGCs arise from progenitors that themselves express cdh6. These progenitors are capable of generating all major retinal cell types, but the RGCs they generate are predominantly of the single direction-selective subtype. In contrast, cdh6-positive progenitors retain the ability to generate multiple subtypes of amacrine and bipolar cells. Our results demonstrate that type and subtype specification are regulated in different ways and suggest that multipotential but fate-restricted progenitors contribute to subtype specification in retina.

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Section: Discussionmentioning

confidence: 58%

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

Huerta

Kim

Voinescu

et al. 2012

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

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“…Interestingly, the clone types produced at E13.5 included HC-only clones. This is an intriguing observation because previous studies in the chick (19) and zebrafish (53) demonstrated that there was a HC-only RPC. In the chick, which has three types of HC (H1, H2, and H3), a terminal division not only produced two HC, but would make two HC of the same type, either two H1 cells or two H3 cells.…”

Section: Discussionmentioning

confidence: 79%

“…3, Table 1, and Dataset S2). Labeled cells were arranged in radial clusters, shown to be clones in previous studies (1,3,19,40). The overall frequencies of cell types present in clones derived from P0 Olig2 + RPCs were skewed from the control set, with enrichment for rod PRs and ACs.…”

Section: Olig2 Expression In Developing Retina During Embryonic and Pmentioning

confidence: 99%

“…Extensive heterogeneity in the expression of many developmental regulators was observed (18). To address whether the molecular heterogeneity among RPCs might correlate with the extensive clonal heterogeneity observed in the previous studies of retrovirally marked clones (3,4,19), we used a unique type of retroviral clonal analysis based upon infection of a defined type of RPC. The method relied upon the specific infection of mitotic cells that expressed the Olig2 basic helix-loop-helix (bHLH) transcription factor.…”

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confidence: 99%

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Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates

Hafler

Surzenko

Beier

et al. 2012

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

133

170

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Previous lineage analyses have shown that retinal progenitor cells (RPCs) are multipotent throughout development, and expressionprofiling studies have shown a great deal of molecular heterogeneity among RPCs. To determine if the molecular heterogeneity predicts that an RPC will produce particular types of progeny, clonal lineage analysis was used to investigate the progeny of a subset of RPCs, those that express the basic helix-loop-helix transcription factor, Olig2. The embryonic Olig2 + RPCs underwent terminal divisions, producing small clones with primarily two of the five cell types being made by the pool of RPCs at that time. The later, postnatal Olig2 + RPCs also made terminal divisions, which were biased toward production of rod photoreceptors and amacrine cell interneurons. These data indicate that the multipotent progenitor pool is made up of distinctive types of RPCs, which have biases toward producing subsets of retinal neurons in a terminal division, with the types of neurons produced varying over time. This strategy is similar to that of the developing Drosophila melanogaster ventral nerve cord, with the Olig2 + cells behaving as ganglion mother cells.neural progenitors | neural development | oligodendrocyte transcription factor 2

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“…The lateral ventricles of E15.5 embryos were injected with 2 lL Qiagen Maxiprep DNA and Fast Green dye using a pulled micropipette. The following plasmids were used: pCMV-LifeAct-TagRFP [51] (3 lg/lL; 60102, ibidi GmbH, Martinsried, Germany), GFP-actinin [52] (3 lg/lL), tdTomato [53] (0.5 lg/lL; 22478, Addgene, Cambridge, MA; originally named FUtdTW), and pCS2 min-GFP [49] (1 lg/lL). Forceps-type electrode paddles controlled by an ECM 830 electroporator (BTX Instrument Division, Harvard Apparatus Inc, Holliston, MA) were used to deliver 5 pulses at 60 mV with 50 ms duration at 100 ms intervals.…”

Section: In Utero Electroporationmentioning

confidence: 99%

Actin Aggregations Mark the Sites of Neurite Initiation

et al. 2016

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A salient feature of neurons is their intrinsic ability to grow and extend neurites, even in the absence of external cues. Compared to the later stages of neuronal development, such as neuronal polarization and dendrite morphogenesis, the early steps of neuritogenesis remain relatively unexplored. Here we showed that redistribution of cortical actin into large aggregates preceded neuritogenesis and determined the site of neurite initiation. Enhancing actin polymerization by jasplakinolide treatment effectively blocked actin redistribution and neurite initiation, while treatment with the actin depolymerizing agents latrunculin A or cytochalasin D accelerated neurite formation. Together, these results demonstrate a critical role of actin dynamics and reorganization in neurite initiation. Further experiments showed that microtubule dynamics and protein synthesis are not required for neurite initiation, but are required for later neurite stabilization. The redistribution of actin during early neuronal development was also observed in the cerebral cortex and hippocampus in vivo.

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Retinal progenitor cells can produce restricted subsets of horizontal cells

Cited by 67 publications

References 28 publications

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

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

Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates

Actin Aggregations Mark the Sites of Neurite Initiation

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