scholarly journals Lineage tracing analysis of cone photoreceptor-associated cis-regulatory elements in the developing chicken retina

2019 ◽  
Author(s):  
Estie Schick ◽  
Sean D. McCaffery ◽  
Erin E. Keblish ◽  
Cassandra Thakurdin ◽  
Mark M. Emerson
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Regulatory Elements ◽  
Lineage Tracing ◽  
Horizontal Cells ◽  
Retinal Ganglion ◽  
Cone Photoreceptors ◽  
Cell Type

During vertebrate retinal development, transient populations of retinal progenitor cells with restricted cell fate choices are formed. One of these progenitor populations expresses the Thrb gene and can be identified with the ThrbCRM1 cis-regulatory element. Short-term assays have concluded that these cells preferentially generate cone photoreceptors and horizontal cells, however developmental timing has precluded an extensive cell type characterization of their progeny. Here we describe the development and validation of a recombinase-based lineage tracing system for the chicken embryo to further characterize the lineage of these cells. The ThrbCRM1 element was found to preferentially form photoreceptors and horizontal cells, as well as a small number of retinal ganglion cells. The photoreceptor cell progeny are exclusively cone photoreceptors and not rod photoreceptors, confirming that ThrbCRM1-progenitor cells are restricted from the rod fate. In addition, specific subtypes of horizontal cells and retinal ganglion cells were overrepresented, suggesting that ThrbCRM1 progenitor cells are not only restricted for cell type, but for cell subtype as well.

scholarly journals Molecular codes for cell type specification in Brn3 retinal ganglion cells

2017 ◽  
Vol 114 (20) ◽  
pp. E3974-E3983 ◽  
Author(s):  
Szilard Sajgo ◽  
Miruna Georgiana Ghinia ◽  
Matthew Brooks ◽  
Friedrich Kretschmer ◽  
Katherine Chuang ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Neuronal Cell ◽  
Neuronal Morphology ◽  
Retinal Ganglion ◽  
Cell Type ◽  
Type Specification ◽  
The Brain ◽  
Combinatorial Code

Visual information is conveyed from the eye to the brain by distinct types of retinal ganglion cells (RGCs). It is largely unknown how RGCs acquire their defining morphological and physiological features and connect to upstream and downstream synaptic partners. The three Brn3/Pou4f transcription factors (TFs) participate in a combinatorial code for RGC type specification, but their exact molecular roles are still unclear. We use deep sequencing to define (i) transcriptomes of Brn3a- and/or Brn3b-positive RGCs, (ii) Brn3a- and/or Brn3b-dependent RGC transcripts, and (iii) transcriptomes of retinorecipient areas of the brain at developmental stages relevant for axon guidance, dendrite formation, and synaptogenesis. We reveal a combinatorial code of TFs, cell surface molecules, and determinants of neuronal morphology that is differentially expressed in specific RGC populations and selectively regulated by Brn3a and/or Brn3b. This comprehensive molecular code provides a basis for understanding neuronal cell type specification in RGCs.

Mitochondrial Optic Neuropathies: How Two Genomes may Kill the Same Cell Type?

2007 ◽  
Vol 27 (1-3) ◽  
pp. 173-184 ◽  
Author(s):  
Valerio Carelli ◽  
Chiara La Morgia ◽  
Luisa Iommarini ◽  
Rosanna Carroccia ◽  
Marina Mattiazzi ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Point Mutations ◽  
Mitochondrial Diseases ◽  
Ocular Involvement ◽  
Retinal Ganglion ◽  
Mitochondrial Network ◽  
Cell Type ◽  
Cellular Targets ◽  
Hereditary Optic Neuropathy

Ocular involvement is a prevalent feature in mitochondrial diseases. Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA) are both non-syndromic optic neuropathies with a mitochondrial etiology. LHON is associated with point mutations in the mitochondrial DNA (mtDNA), which affect subunit genes of complex I. The majority of DOA patients harbor mutations in the nuclear-encoded protein OPA1, which is targeted to mitochondria and participates to cristae organization and mitochondrial network dynamics. In both disorders the retinal ganglion cells (RGCs) are specific cellular targets of the degenerative process. We here review the clinical features and the genetic bases, and delineate the possible common pathomechanism for both these disorders.

scholarly journals Adaptation in cone photoreceptors contributes to an unexpected insensitivity of On parasol retinal ganglion cells to spatial structure in natural images

2021 ◽  
Author(s):  
Zhou Yu ◽  
Maxwell H Turner ◽  
Fred Rieke
Keyword(s):  
Spatial Structure ◽  
Retinal Ganglion Cells ◽  
Neural Circuits ◽  
Ganglion Cells ◽  
Nonlinear Behavior ◽  
Building Blocks ◽  
Retinal Ganglion ◽  
Cone Photoreceptors ◽  
Strongly Nonlinear ◽  
Visual Inputs

Neural circuits are constructed from nonlinear building blocks, and not surprisingly overall circuit behavior is often strongly nonlinear. But neural circuits can also behave near linearly, and some circuits shift from linear to nonlinear behavior depending on stimulus conditions. Such control of the linearity or nonlinearity of circuit behavior is fundamental to neural computation. Here we study a surprising stimulus dependence of the responses of On (but not Off) parasol retinal ganglion cells: these cells respond nonlinearly to spatial structure in temporally-modulated grating stimuli but linearly to spatial structure in flashed gratings and natural visual inputs. We show that this unexpected response linearity can be explained by a shift in the balance of excitatory and inhibitory synaptic inputs that originates at least in part from adaptation in the cone photoreceptors. More generally, this highlights how subtle asymmetries in signaling - here in the cone signals - can qualitatively alter circuit computation.

scholarly journals De novo genesis of retinal ganglion cells by targeted expression of KLF4 in vivo

2018 ◽  
Author(s):  
Maurício Rocha-Martins ◽  
Beatriz C. de Toledo ◽  
Pedro L. Santos-França ◽  
Viviane M. Oliveira-Valença ◽  
Carlos H. Vieira-Vieira ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Progenitor Cells ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Müller Cells ◽  
Therapeutic Strategies ◽  
Retinal Ganglion ◽  
Promising Tool ◽  
Irreversible Blindness

AbstractRetinal ganglion cell (RGC) degeneration is a hallmark of glaucoma, the most prevalent cause of irreversible blindness. Thus, innovative therapeutic strategies are needed to protect and replace these projection neurons. It has been shown that endogenous glial cells of the retina, Müller cells, can be directly reprogrammed into late-born retinal interneurons. However, since RGCs are the first neurons born during development, the replacement of damaged RGCs requires the reprograming to an early neurogenic state. Here, we demonstrate that the pluripotency regulator Klf4 is sufficient to reprogram the potency of lineage-restricted retinal progenitor cells (RPCs) to generate RGCs in vivo. Transcriptome analysis disclosed that the overexpression of Klf4 induces crucial regulators of RGC competence and specification, including Atoh7 and Eya2. In contrast, loss-of-function studies in mice and zebrafish demonstrated that Klf4 is not essential for generation or differentiation of RGCs during retinogenesis. Nevertheless, induced RGCs (iRGCs) generated upon Klf4 overexpression migrate to the proper layer and project axons aligned with endogenous fascicles that reach the optic nerve head. Notably, iRGCs survive for up to 30 days after in vivo reprogramming. Finally, we demonstrate that Klf4 converts Müller cells into neurons that express markers of RGCs. Altogether, we identified Klf4 as a promising tool to reprogram retinal cells and regenerate RGCs in the mature retina.Significance StatementCell fate determination is a key process for development, regeneration and for the design of therapeutic strategies that involve cellular reprogramming. This work shows that the manipulation of a single pluripotency regulator (Klf4) is sufficient to reprogram restricted progenitor cells in vivo. These reprogrammed progenitors reacquire the potency to generate retinal ganglion cells. Ganglion cell degeneration is the leading cause of irreversible blindness; therefore, manipulation of ganglion cell competence is of relevance for human health. Our findings point to Klf4 as a promising tool to develop therapeutic strategies for the replacement of damaged ganglion cells.

Categorization of Physiologically and Morphologically Characterized non-α/non-β Cat Retinal Ganglion Cells Using Fractal Geometry

Fractals ◽  
1997 ◽  
Vol 05 (04) ◽  
pp. 673-684 ◽  
Author(s):  
H. F. Jelinek ◽  
I. Spence
Keyword(s):  
Fractal Dimension ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Cell Type ◽  
Box Counting ◽  
Standard Values ◽  
Box Counting Method ◽  
Delta Cells

Non-α/non-β cat retinal ganglion cell images were obtained from the published literature, and a homogeneous group of cells was chosen as a standard for each currently accepted cell type (γ, δ and ε). The NIH box-counting method was chosen to determine the fractal dimension (Df) of all cells. The 'standard' values allowed comparisons with other morphologically and physiologically non-α/non-β classified cell types in the literature. We suggest, based on fractal analysis of the dendritic trees, that the morphologically defined γ, δ, and ε cells are distinct types. The W-tonic and W-phasic cell types were further divided into 2 subcategories (W-tonic1, W-tonic2, W-phasic1, W-phasic2). The fractal dimension, of the ε cells being equivalent to the W-tonic1 group and γ cell type equivalent to the W-phasic1 group. Delta cells may be equivalent to either the W-tonic2 or the W-phasic2 group. We discuss the value of the fractal dimension as an added morphological parameter for future morphophysiological classification schemes of vertebrate retinal ganglion cells.

Enriched populations of rat retinal ganglion cells: Studies using a cell-type specific surface marker

1983 ◽  
Vol 5 (6) ◽  
pp. 691-696 ◽  
Author(s):  
Richard Beale ◽  
David W. Beaton ◽  
Volker Neuhoff ◽  
Neville N. Osborne
Keyword(s):  
Specific Surface ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Surface Marker ◽  
Retinal Ganglion ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific
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