Ligands of steroid/thyroid receptors induce cone photoreceptors in vertebrate retina

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3777-3785 ◽  
Author(s):  
M.W. Kelley ◽  
J.K. Turner ◽  
T.A. Reh
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Rod Photoreceptor ◽  
Cone Photoreceptors ◽  
Retinoid Receptor ◽  
Signaling Systems ◽  
Multipotent Progenitor Cells ◽  
Vertebrate Central Nervous System

The mechanisms by which multipotent progenitor cells are directed to alternative cell identities during the histogenesis of the vertebrate central nervous system are likely to involve several different types of signaling systems. Recent evidence indicates that 9-cis retinoic acid, which acts through members of the steroid/thyroid superfamily of receptors, directs progenitor cells to the rod photoreceptor cell fate. We now report that another effector of this family of receptors, thyroid hormone, induces an increase in the number of cone photoreceptors that develop in embryonic rat retinal cultures, and that combinations of 9-cis retinoic acid and triiodothyronine cause isolated progenitor cells to differentiate as either rods or cones, depending on the relative concentrations of the ligands. These results implicate thyroid hormone in CNS cell fate determination, and suggest that different photoreceptor phenotypes may be modulated through the formation of thyroid/retinoid receptor heterodimers.

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.

Sequential specification of neurons and glia by developmentally regulated extracellular factors

Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3585-3594 ◽  
Author(s):  
Theresa Morrow ◽  
Mi-Ryoung Song ◽  
Anirvan Ghosh
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Developmental Stages ◽  
Developmentally Regulated ◽  
Fate Specification ◽  
Multipotent Progenitor Cells ◽  
Glial Fate ◽  
Sequential Generation ◽  
Cortical Slices ◽  
Cortical Progenitor

Cortical progenitor cells give rise to neurons during embryonic development and to glia after birth. While lineage studies indicate that multipotent progenitor cells are capable of generating both neurons and glia, the role of extracellular signals in regulating the sequential differentiation of these cells is poorly understood. To investigate how factors in the developing cortex might influence cell fate, we developed a cortical slice overlay assay in which cortical progenitor cells are cultured over cortical slices from different developmental stages. We find that embryonic cortical progenitors cultured over embryonic cortical slices differentiate into neurons and those cultured over postnatal cortical slices differentiate into glia, suggesting that the fate of embryonic progenitors can be influenced by developmentally regulated signals. In contrast, postnatal progenitor cells differentiate into glial cells when cultured over either embryonic or postnatal cortical slices. Clonal analysis indicates that the postnatal cortex produces a diffusible factor that induces progenitor cells to adopt glial fates at the expense of neuronal fates. The effects of the postnatal cortical signals on glial cell differentiation are mimicked by FGF2 and CNTF, which induce glial fate specification and terminal glial differentiation respectively. These observations indicate that cell fate specification and terminal differentiation can be independently regulated and suggest that the sequential generation of neurons and glia in the cortex is regulated by a developmental increase in gliogenic signals.

COUP orphan receptors are negative regulators of retinoic acid response pathways

1992 ◽  
Vol 12 (10) ◽  
pp. 4666-4676
Author(s):  
P Tran ◽  
X K Zhang ◽  
G Salbert ◽  
T Hermann ◽  
J M Lehmann ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Nuclear Receptors ◽  
Thyroid Hormone Receptor ◽  
Cdna Probe ◽  
Specific Response ◽  
Retinoid Receptor ◽  
Orphan Receptors ◽  
Response Element ◽  
Response Elements

The vitamin hormone retinoic acid (RA) regulates many complex biological programs. The hormonal signals are mediated at the level of transcription by multiple nuclear receptors. These receptors belong to the steroid/thyroid hormone receptor superfamily that also includes a large number of orphan receptors whose biological roles have not yet been determined. Although much has been learned in recent years about RA receptor (RAR) functions, little is known about how specific RA response programs are restricted to certain tissues and cell types during development and in the adult. It has been recently shown that RAR activities are regulated by retinoid X receptors (RXR) through heterodimer formation. In an effort to isolate and further characterize nuclear receptors that modulate RAR and/or RXR activities, we have screened cDNA libraries by using a RXR alpha cDNA probe. Two clones, COUP alpha and COUP beta, identical and closely related to the orphan receptor COUP-TF, were obtained. We show that COUP proteins dramatically inhibit retinoid receptor activities on certain response elements that are activated by RAR/RXR heterodimers or RXR homodimers. COUP alpha and -beta bind strongly to these response elements, including a palindromic thyroid hormone response element and a direct repeat RA response element as well as an RXR-specific response element. In addition, we found that the previously identified COUP-TF binding site in the ovalbumin gene functions in vitro as an RA response element that is repressed in the presence of COUP. Our data suggest that the COUP receptors are a novel class of RAR and RXR regulators that can restrict RA signaling to certain elements. The COUP orphan receptors may thus play an important role in cell- or tissue-specific repression of subsets of RA-sensitive programs during development and in the adult.

scholarly journals COUP orphan receptors are negative regulators of retinoic acid response pathways.

1992 ◽  
Vol 12 (10) ◽  
pp. 4666-4676 ◽  
Author(s):  
P Tran ◽  
X K Zhang ◽  
G Salbert ◽  
T Hermann ◽  
J M Lehmann ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Nuclear Receptors ◽  
Thyroid Hormone Receptor ◽  
Cdna Probe ◽  
Specific Response ◽  
Retinoid Receptor ◽  
Orphan Receptors ◽  
Response Element ◽  
Response Elements

The vitamin hormone retinoic acid (RA) regulates many complex biological programs. The hormonal signals are mediated at the level of transcription by multiple nuclear receptors. These receptors belong to the steroid/thyroid hormone receptor superfamily that also includes a large number of orphan receptors whose biological roles have not yet been determined. Although much has been learned in recent years about RA receptor (RAR) functions, little is known about how specific RA response programs are restricted to certain tissues and cell types during development and in the adult. It has been recently shown that RAR activities are regulated by retinoid X receptors (RXR) through heterodimer formation. In an effort to isolate and further characterize nuclear receptors that modulate RAR and/or RXR activities, we have screened cDNA libraries by using a RXR alpha cDNA probe. Two clones, COUP alpha and COUP beta, identical and closely related to the orphan receptor COUP-TF, were obtained. We show that COUP proteins dramatically inhibit retinoid receptor activities on certain response elements that are activated by RAR/RXR heterodimers or RXR homodimers. COUP alpha and -beta bind strongly to these response elements, including a palindromic thyroid hormone response element and a direct repeat RA response element as well as an RXR-specific response element. In addition, we found that the previously identified COUP-TF binding site in the ovalbumin gene functions in vitro as an RA response element that is repressed in the presence of COUP. Our data suggest that the COUP receptors are a novel class of RAR and RXR regulators that can restrict RA signaling to certain elements. The COUP orphan receptors may thus play an important role in cell- or tissue-specific repression of subsets of RA-sensitive programs during development and in the adult.

Subsets of retinal progenitors display temporally regulated and distinct biases in the fates of their progeny

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1119-1131 ◽  
Author(s):  
M.R. Alexiades ◽  
C.L. Cepko
Keyword(s):  
Progenitor Cells ◽  
Cell Fate ◽  
Retinal Development ◽  
Amacrine Cells ◽  
Antigen Expression ◽  
Cell Types ◽  
Postnatal Period ◽  
Horizontal Cells ◽  
Cone Photoreceptors ◽  
Multipotent Progenitors

Cell fate determination in the developing vertebrate retina is characterized by the sequential generation of seven classes of cells by multipotent progenitor cells. Despite this order of genesis, more than one cell type is generated at any time; for example, in the rat, several cell types are born during the prenatal period, while others are born postnatally. In order to examine whether there are classes of progenitor cells with distinct developmental properties contributing to this developmental progression, we examined antigen expression in progenitor cells during rat retinal development. Two markers of amacrine and horizontal cells, the VC1.1 epitope and syntaxin, were found to be expressed on a subset of progenitors in a temporally regulated manner that closely paralleled the birthdays of these cell types. In order to investigate which cell types were produced by the progenitors expressing these markers, fluorescent latex microspheres covalently coupled to VC1.1 antibodies were used to indelibly label VC1.1+ progenitor cells and their progeny. Early in retinal development, VC1.1+ progenitors generated a high percentage of amacrine and horizontal cells, but no cone photoreceptors. During this same period, a comparable number of cone photoreceptors were generated by VC1.1- progenitors. In the late embryonic and early postnatal period, VC1.1+ progenitors continued to generate predominantly amacrine cells, but also gave rise to an increasing number of rod photoreceptors. These findings demonstrate that expression of these two markers by progenitors is highly correlated with a bias towards the production of amacrine and horizontal cells. The fact that subsets of progenitors with temporally regulated and distinct biases are intermingled within the retinal neuroepithelium provides a basis for understanding how different cell types are generated both simultaneously and in a particular order by multipotent progenitors during retinal development.

scholarly journals Cell fate-decision as high-dimensional critical state transition

2016 ◽  
Author(s):  
Mitra Mojtahedi ◽  
Alexander Skupin ◽  
Joseph Zhou ◽  
Ivan G. Castaño ◽  
Rebecca Y. Y. Leong-Quong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Critical State ◽  
State Transition ◽  
High Dimensional ◽  
Critical Transitions ◽  
Formal Tool ◽  
Multipotent Progenitor Cells ◽  
Fate Decision

AbstractCell fate choice and commitment of multipotent progenitor cells to a differentiated lineage requires broad changes of their gene expression profile. However, how progenitor cells overcome the stability of their robust gene expression configuration (attractor) and exit their state remains elusive. Here we show that commitment of blood progenitor cells to the erythroid or the myeloid lineage is preceded by the destabilization of their high-dimensional attractor state and that cells undergo a critical state transition. Single-cell resolution analysis of gene expression in populations of differentiating cells affords a new quantitative index for predicting critical transitions in a high-dimensional state space: decrease of correlation between cells with concomitant increase of correlation between genes as cells approach a tipping point. The detection of “rebellious cells” which enter the fate opposite to the one intended corroborates the model of preceding destabilization of the progenitor state. Thus, “early-warning signals” associated with critical transitions can be detected in statistical ensembles of high-dimensional systems, offering a formal tool for analyzing single-cell’s molecular profiles that goes beyond computational pattern recognition but is based on dynamical systems theory and can predict impending major shifts in cell populations in development and disease.

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