scholarly journals Pou2f1 and Pou2f2 cooperate to control the timing of cone photoreceptor production in the developing mouse retina

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev188730 ◽  
Author(s):  
Awais Javed ◽  
Pierre Mattar ◽  
Suying Lu ◽  
Kamil Kruczek ◽  
Magdalena Kloc ◽  
...  
Keyword(s):  
Cell Types ◽  
Mouse Retina ◽  
Cone Photoreceptor ◽  
Chronological Order ◽  
Temporal Window ◽  
General Role ◽  
Cone Production ◽  
Regulatory Cascade ◽  
The People ◽  
Temporal Identity

ABSTRACTMultipotent retinal progenitor cells (RPCs) generate various cell types in a precise chronological order, but how exactly cone photoreceptor production is restricted to early stages remains unclear. Here, we show that the POU-homeodomain factors Pou2f1/Pou2f2, the homologs of Drosophila temporal identity factors nub/pdm2, regulate the timely production of cones in mice. Forcing sustained expression of Pou2f1 or Pou2f2 in RPCs expands the period of cone production, whereas misexpression in late-stage RPCs triggers ectopic cone production at the expense of late-born fates. Mechanistically, we report that Pou2f1 induces Pou2f2 expression, which binds to a POU motif in the promoter of the rod-inducing factor Nrl to repress its expression. Conversely, conditional inactivation of Pou2f2 in RPCs increases Nrl expression and reduces cone production. Finally, we provide evidence that Pou2f1 is part of a cross-regulatory cascade with the other temporal identity factors Ikzf1 and Casz1. These results uncover Pou2f1/2 as regulators of the temporal window for cone genesis and, given their widespread expression in the nervous system, raise the possibility of a general role in temporal patterning.This article has an associated ‘The people behind the papers’ interview.

scholarly journals The people behind the papers – Awais Javed and Michel Cayouette

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev196469
Keyword(s):  
Clinical Research ◽  
Progenitor Cells ◽  
Cell Types ◽  
Research Unit ◽  
Chronological Order ◽  
The People ◽  
Distinct Cell ◽  
Mammalian Retina ◽  
Mcgill University

ABSTRACTThe mammalian retina contains a variety of functionally distinct cell types that are generated by progenitor cells in a specific chronological order. A new paper in Development probes the role of the POU-homeodomain factors Pou2f1 and Pou2f2 in the timely generation of cone photoreceptors in mice. We caught up with first author and PhD student Awais Javed and his supervisor Michel Cayouette (Director of the Cellular Neurobiology Research Unit at the Montreal Clinical Research Institute, Professor at the Université de Montréal and Adjunct Professor at McGill University) to hear more about their work.

scholarly journals Enhancer transcription identifies cis-regulatory elements for photoreceptor cell types

2019 ◽  
Author(s):  
Rangarajan D. Nadadur ◽  
Carlos Perez-Cervantes ◽  
Nicolas Lonfat ◽  
Linsin A. Smith ◽  
Andrew E. O. Hughes ◽  
...  
Keyword(s):  
Differential Expression ◽  
Regulatory Networks ◽  
Photoreceptor Cell ◽  
Cell Types ◽  
Regulatory Elements ◽  
Mouse Retina ◽  
Specific Cell ◽  
Rod Photoreceptor ◽  
Cone Photoreceptor ◽  
Accessible Chromatin

AbstractIdentification of the cis-regulatory elements (CREs) that regulate gene expression in specific cell types is critical for defining the gene regulatory networks (GRNs) that control normal physiology and disease states. We previously utilized non-coding RNA (ncRNA) profiling to define CREs that comprise a GRN in the adult mouse heart1. Here, we applied ncRNA profiling to the mouse retina in the presence and absence of Nrl, a rod photoreceptor-specific transcription factor required for rod versus cone photoreceptor cell fate. Differential expression of Nrl-dependent ncRNAs positively correlated with differential expression of Nrl-dependent local genes. Two distinct Nrl-dependent regulatory networks were discerned in parallel: Nrl-activated ncRNAs were enriched for accessible chromatin in rods but not cones whereas Nrl-repressed ncRNAs were enriched for accessible chromatin in cones but not rods. Furthermore, differential Nrl-dependent ncRNA expression levels quantitatively correlated with photoreceptor cell type-specific ATAC-seq read density. Direct assessment of Nrl-dependent ncRNA-defined loci identified functional cone photoreceptor CREs. This work supports differential ncRNA profiling as a platform for identifying context-specific regulatory elements and provides insight into the networks that define photoreceptor cell types.

The Professional Life of Clayton Paul Alderfer

2017 ◽  
Vol 53 (2) ◽  
pp. 156-179
Author(s):  
David N. Berg ◽  
Kenwyn K. Smith
Keyword(s):  
Race Relations ◽  
Intergroup Relations ◽  
Early Adulthood ◽  
Adult Life ◽  
Professional Life ◽  
Chronological Order ◽  
Late Adulthood ◽  
Left Behind ◽  
Embedded Intergroup Relations ◽  
The People

Clayton Paul Alderfer died on October 30, 2015. In addition to the people he left behind (family, friends, colleagues, and former students), Clay also bequeathed a richly varied scholarly legacy. This article introduces the reader to Alderfer’s life and work. Since Alderfer believed that one’s work is influenced by one’s stage of life, his work is presented in chronological order from early adulthood through late adulthood. What emerges is a picture of how the major intellectual themes he worked on—need theory, embedded intergroup relations, organizational diagnosis, and race relations—developed over the course of his adult life. Alderfer is presented in his own words, sentences and paragraphs excerpted from his published legacy, to minimize interpretation and maximize the reader’s exposure to the man and his ideas.

scholarly journals A QTL on Chromosome 10 Modulates Cone Photoreceptor Number in the Mouse Retina

2011 ◽  
Vol 52 (6) ◽  
pp. 3228 ◽  
Author(s):  
Irene E. Whitney ◽  
Mary A. Raven ◽  
Lu Lu ◽  
Robert W. Williams ◽  
Benjamin E. Reese
Keyword(s):  
Mouse Retina ◽  
Cone Photoreceptor ◽  
Chromosome 10

scholarly journals Direct neuronal reprogramming by temporal identity factors

2021 ◽  
Author(s):  
Camille Boudreau-Pinsonneault ◽  
Awais Javed ◽  
Michel Fries ◽  
Pierre Mattar ◽  
Michel Cayouette
Keyword(s):  
Gene Expression ◽  
Expression System ◽  
Lineage Tracing ◽  
Developmental Competence ◽  
Rapid Screening ◽  
Mouse Retina ◽  
Genetic Lineage ◽  
Differentiated Cells ◽  
Temporal Identity

Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors, but whether they could also reprogram the identity of fully differentiated cells is unknown. To address this question, we designed a conditional gene expression system combined with genetic lineage tracing that allows rapid screening of potential reprogramming factors in the mouse retina. Using this assay, we report that co-expression of the early temporal identity transcription factor Ikzf1, together with Ikzf4, another Ikaros family member, is sufficient to directly convert adult Muller glial cells into neuron-like cells in vivo, without inducing a proliferative progenitor state. scRNA-seq analysis shows that the reprogrammed cells share some transcriptional signatures with both cone photoreceptors and bipolar cells. Furthermore, we show that co-expression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons by remodeling chromatin and promoting a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in differentiated cells, opening new opportunities for cell therapy development.

Developmental expression of Sp1 in the mouse

1991 ◽  
Vol 11 (4) ◽  
pp. 2189-2199
Author(s):  
J D Saffer ◽  
S P Jackson ◽  
M B Annarella
Keyword(s):  
Housekeeping Genes ◽  
Cell Types ◽  
Immunohistochemical Localization ◽  
Developmental Expression ◽  
Regulatory Function ◽  
General Role ◽  
Protein Levels ◽  
Rna Analysis ◽  
Different Cell Types ◽  
Unexpected Difference

The expression of the trans-acting transcription factor Sp1 in mice was defined by a combination of RNA analysis and immunohistochemical localization of the Sp1 protein. Although ubiquitously expressed, there was an unexpected difference of at least 100-fold in the amount of Sp1 message in different cell types. Sp1 protein levels showed corresponding marked differences. Substantial variations in Sp1 expression were also found in some cell types at different stages of development. Sp1 levels appeared to be highest in developing hematopoietic cells, fetal cells, and spermatids, suggesting that an elevated Sp1 level is associated with the differentiation process. These results indicate that Sp1 has a regulatory function in addition to its general role in the transcription of housekeeping genes.

scholarly journals The people behind the papers – Kayt Scott and Bruce Appel

Development ◽  
2020 ◽  
Vol 147 (16) ◽  
pp. dev195735
Keyword(s):  
Motor Neurons ◽  
Cell Biology ◽  
Zebrafish Embryo ◽  
Cell Types ◽  
Colorado School ◽  
Molecular Control ◽  
University Of Colorado ◽  
School Of Medicine ◽  
The People ◽  
Developing Spinal Cord

ABSTRACTIn the developing spinal cord, progenitor cells sequentially give rise to motor neurons and precursors of one of the major glial cell types: oligodendrocytes. A new paper in Development unpicks the molecular control of the neuron-glia switch and the differentiation of oligodendrocyte precursors in the zebrafish embryo. To find out more about the work, we met first author and graduate student Kayt Scott and her supervisor Bruce Appel, who holds the Diane G. Wallach Chair of Pediatric Stem Cell Biology and is Professor and Head of the Section of Developmental Biology at the Department of Pediatrics, University of Colorado School of Medicine in Aurora.

scholarly journals Laminin deficits induce alterations in the development of dopaminergic neurons in the mouse retina

2007 ◽  
Vol 24 (4) ◽  
pp. 549-562 ◽  
Author(s):  
VIKTÓRIA DÉNES ◽  
PAUL WITKOVSKY ◽  
MANUEL KOCH ◽  
DALE D. HUNTER ◽  
GERMÁN PINZÓN-DUARTE ◽  
...  
Keyword(s):  
Amacrine Cells ◽  
Cell Types ◽  
Mouse Retina ◽  
Null Mouse ◽  
Type I ◽  
Intermediate Cell ◽  
Retinal Ganglion ◽  
Wild Type ◽  
Müller Glial Cell ◽  
Process Outgrowth

Genetically modified mice lacking the β2 laminin chain (β2null), the γ3 laminin chain (γ3 null), or both β2/γ3 chains (compound null) were produced. The development of tyrosine hydroxylase (TH) immunoreactive neurons in these mouse lines was studied between birth and postnatal day (P) 20. Compared to wild type mice, no alterations were seen in γ3 null mice. In β2 null mice, however, the large, type I TH neurons appeared later in development, were at a lower density and had reduced TH immunoreactivity, although TH process number and size were not altered. In the compound null mouse, the same changes were observed together with reduced TH process outgrowth. Surprisingly, in the smaller, type II TH neurons, TH immunoreactivity was increased in laminin-deficient compared to wild type mice. Other retinal defects we observed were a patchy disruption of the inner limiting retinal basement membrane and a disoriented growth of Müller glial cells. Starburst and AII type amacrine cells were not apparently altered in laminin-deficient relative to wild type mice. We postulate that laminin-dependent developmental signals are conveyed to TH amacrine neurons through intermediate cell types, perhaps the Müller glial cell and/or the retinal ganglion cell.

scholarly journals Regulation of H2O2 generation in thyroid cells does not involve Rac1 activation

2005 ◽  
Vol 152 (1) ◽  
pp. 127-133 ◽  
Author(s):  
N Fortemaison ◽  
F Miot ◽  
J E Dumont ◽  
S Dremier
Keyword(s):  
Phorbol Ester ◽  
Cell Types ◽  
Glutathione S Transferase ◽  
Thyroid Cells ◽  
Toxin B ◽  
Regulatory Cascade ◽  
Nox Family ◽  
Design And Methods ◽  
Generating System ◽  
Stimulation Of

Objectives: The H2O2 generating system of the thyrocyte and the O2− generating system of macrophages and leukocytes present numerous functional analogies. The main constituent enzymes belong to the NADPH oxidase (NOX) family (Duox/ThOX for the thyroid and NOX2/gp91phox for the leukocytes and macrophages), and in both cell types, H2O2 generation is activated by the intra-cellular generation of Ca2+ and diacylglycerol signals. Nevertheless, although the controls involved in these two systems are similar, their mechanisms are different. The main factors controlling O2− production by NOX2 are the cytosolic proteins p67phox and p47phox, and Rac, a small GTP-binding protein. We have previously reported that there is no expression of p67phox and p47phox in thyrocytes. Here, we investigated whether Rac1 is an actor in the thyroid H2O2-generating system. Design and methods: Ionomycin- and carbamylcholine-stimulated H2O2 generation was measured in dog thyroid cells pretreated with the Clostridium difficile toxin B, which inhibits Rac proteins. Activation of Rac1 was measured in response to agents stimulating H2O2 production, using the CRIB domain of PAK1 as a probe in a glutathione S-transferase (GST) pull-down assay. Results: Among the various agents inducing H2O2 generation in dog thyrocytes, carbamylcholine is the only one which activates Rac1, whereas phorbol ester and calcium increase alone have no effect, and cAMP inactivates it. Moreover, whereas toxin B inhibits the stimulation of O2 generation by phorbol ester in leukocytes, it does not inhibit H2O2 generation induced by carbamylcholine and ionomycin in dog thyrocytes. Conclusions: Unlike in leukocytes, Rac proteins do not play a role in H2O2 generation in thyroid cells. A different regulatory cascade for the control of H2O2 generation remains to be defined.

scholarly journals DSCAM and DSCAML1 Function in Self-Avoidance in Multiple Cell Types in the Developing Mouse Retina

Neuron ◽  
2009 ◽  
Vol 64 (4) ◽  
pp. 484-497 ◽  
Author(s):  
Peter G. Fuerst ◽  
Freyja Bruce ◽  
Miao Tian ◽  
Wei Wei ◽  
Justin Elstrott ◽  
...  
Keyword(s):  
Cell Types ◽  
Mouse Retina ◽  
Multiple Cell
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