scholarly journals Modeling binary and graded cone cell fate patterning in the mouse retina

2019 ◽  
Author(s):  
Kiara C. Eldred ◽  
Cameron Avelis ◽  
Robert J. Johnston ◽  
Elijah Roberts
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Cell Fate ◽  
Regulatory Network ◽  
Photoreceptor Cells ◽  
Mouse Retina ◽  
Hormone Signaling ◽  
Cell Fates ◽  
Opsin Expression ◽  
A Cell

AbstractNervous systems are incredibly diverse, with myriad neuronal subtypes defined by gene expression. How binary and graded fate characteristics are patterned across tissues is poorly understood. Expression of opsin photopigments in the cone photoreceptors of the mouse retina provides an excellent model to address this question. Individual cones express S-opsin only, M-opsin, or both S-opsin and M-opsin. These cell populations are patterned along the dorsal-ventral axis, with greater M-opsin expression in the dorsal region and greater S-opsin expression in the ventral region. Thyroid hormone signaling plays a critical role in activating M-opsin and repressing S-opsin. Here, we developed an image analysis approach to identify individual cone cells and evaluate their opsin expression from immunofluorescence imaging tiles spanning roughly 6 mm along the D-V axis of the mouse retina. From analyzing the opsin expression of ∼250,000 cells, we found that cones make a binary decision between S-opsin only and co-expression competent fates. Co-expression competent cells express graded levels of S- and M-opsins, depending nonlinearly on their position in the dorsal-ventral axis. M- and S-opsin expression display differential, inverse patterns. Using these single-cell data we developed a quantitative, stochastic model of cone cell decisions in the retinal tissue based on thyroid hormone signaling activity. The model recovers the probability distribution for cone fate patterning in the mouse retina and describes a minimal set of interactions that are necessary to reproduce the observed cell fates. Our study provides a paradigm describing how differential responses to regulatory inputs generate complex patterns of binary and graded cell fates.Author SummaryThe development of a cell in a mammalian tissue is governed by a complex regulatory network that responds to many input signals to give the cell a distinct identity, a process referred to as cell-fate specification. Some of these cell fates have binary on-or-off gene expression patterns, while others have graded gene expression that changes across the tissue. Differentiation of the photoreceptor cells that sense light in the mouse retina provides a good example of this process. Here, we explore how complex patterns of cell fates are specified in the mouse retina by building a computational model based on analysis of a large number of photoreceptor cells from microscopy images of whole retinas. We use the data and the model to study what exactly it means for a cell to have a binary or graded cell fate and how these cell fates can be distinguished from each other. Our study shows how tens-of-thousands of individual photoreceptor cells can be patterned across a complex tissue by a regulatory network, creating a different outcome depending upon the received inputs.

scholarly journals Thyroid Hormone Signaling in the Mouse Retina

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0168003 ◽  
Author(s):  
Patrick Arbogast ◽  
Frédéric Flamant ◽  
Pierre Godement ◽  
Martin Glösmann ◽  
Leo Peichl
Keyword(s):  
Thyroid Hormone ◽  
Mouse Retina ◽  
Hormone Signaling

Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3865-3876
Author(s):  
M.S. Rones ◽  
K.A. McLaughlin ◽  
M. Raffin ◽  
M. Mercola
Keyword(s):  
Gene Expression ◽  
Notch Signaling ◽  
Cell Fate ◽  
Notch Pathway ◽  
Cell Types ◽  
Myocardial Cell ◽  
Dominant Negative ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Heart Field

Notch signaling mediates numerous developmental cell fate decisions in organisms ranging from flies to humans, resulting in the generation of multiple cell types from equipotential precursors. In this paper, we present evidence that activation of Notch by its ligand Serrate apportions myogenic and non-myogenic cell fates within the early Xenopus heart field. The crescent-shaped field of heart mesoderm is specified initially as cardiomyogenic. While the ventral region of the field forms the myocardial tube, the dorsolateral portions lose myogenic potency and form the dorsal mesocardium and pericardial roof (Raffin, M., Leong, L. M., Rones, M. S., Sparrow, D., Mohun, T. and Mercola, M. (2000) Dev. Biol., 218, 326–340). The local interactions that establish or maintain the distinct myocardial and non-myocardial domains have never been described. Here we show that Xenopus Notch1 (Xotch) and Serrate1 are expressed in overlapping patterns in the early heart field. Conditional activation or inhibition of the Notch pathway with inducible dominant negative or active forms of the RBP-J/Suppressor of Hairless [Su(H)] transcription factor indicated that activation of Notch feeds back on Serrate1 gene expression to localize transcripts more dorsolaterally than those of Notch1, with overlap in the region of the developing mesocardium. Moreover, Notch pathway activation decreased myocardial gene expression and increased expression of a marker of the mesocardium and pericardial roof, whereas inhibition of Notch signaling had the opposite effect. Activation or inhibition of Notch also regulated contribution of individual cells to the myocardium. Importantly, expression of Nkx2. 5 and Gata4 remained largely unaffected, indicating that Notch signaling functions downstream of heart field specification. We conclude that Notch signaling through Su(H) suppresses cardiomyogenesis and that this activity is essential for the correct specification of myocardial and non-myocardial cell fates.

scholarly journals Opposing effects of Wnt/β-catenin signaling on epithelial and mesenchymal cell fate in the developing cochlea

Development ◽  
2021 ◽  
Vol 148 (11) ◽  
Author(s):  
Sara E. Billings ◽  
Nina M. Myers ◽  
Lee Quiruz ◽  
Alan G. Cheng
Keyword(s):  
Cell Fate ◽  
Mesenchymal Cell ◽  
Lateral Wall ◽  
Mesenchymal Cells ◽  
Sensory Cells ◽  
Dependent Manner ◽  
Cell Fates ◽  
Proliferation And Differentiation ◽  
A Cell ◽  
Opposing Effects

ABSTRACT During embryonic development, the otic epithelium and surrounding periotic mesenchymal cells originate from distinct lineages and coordinate to form the mammalian cochlea. Epithelial sensory precursors within the cochlear duct first undergo terminal mitosis before differentiating into sensory and non-sensory cells. In parallel, periotic mesenchymal cells differentiate to shape the lateral wall, modiolus and pericochlear spaces. Previously, Wnt activation was shown to promote proliferation and differentiation of both otic epithelial and mesenchymal cells. Here, we fate-mapped Wnt-responsive epithelial and mesenchymal cells in mice and found that Wnt activation resulted in opposing cell fates. In the post-mitotic cochlear epithelium, Wnt activation via β-catenin stabilization induced clusters of proliferative cells that dedifferentiated and lost epithelial characteristics. In contrast, Wnt-activated periotic mesenchyme formed ectopic pericochlear spaces and cell clusters showing a loss of mesenchymal and gain of epithelial features. Finally, clonal analyses via multi-colored fate-mapping showed that Wnt-activated epithelial cells proliferated and formed clonal colonies, whereas Wnt-activated mesenchymal cells assembled as aggregates of mitotically quiescent cells. Together, we show that Wnt activation drives transition between epithelial and mesenchymal states in a cell type-dependent manner.

scholarly journals The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

2021 ◽  
Author(s):  
Josh Saul ◽  
Takashi Hirose ◽  
Robert Horvitz
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Fate ◽  
Transcriptional Corepressor ◽  
Cell Identity ◽  
C Elegans ◽  
Dna Binding Specificity ◽  
A Cell ◽  
Transcriptional Corepressors ◽  
And Function

Cell identity is characterized by a distinct combination of gene expression, cell morphology and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in older worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.

scholarly journals The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3187-3195 ◽  
Author(s):  
E.P. Spana ◽  
C.Q. Doe
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Fate ◽  
Daughter Cell ◽  
Cell Cortex ◽  
Cell Fates ◽  
Extrinsic Factors ◽  
Cortical Localization ◽  
Ganglion Mother Cell ◽  
Intrinsic And Extrinsic Factors

Both intrinsic and extrinsic factors are known to regulate sibling cell fate. Here we describe a novel mechanism for the asymmetric localization of a transcription factor to one daughter cell at mitosis. The Drosophila CNS develops from asymmetrically dividing neuroblasts, which give rise to a large neuroblast and a smaller ganglion mother cell (GMC). The prospero gene encodes a transcription factor necessary for proper GMC gene expression. We show that the prospero protein is synthesized in the neuroblast where it is localized to the F-actin cell cortex. At mitosis, prospero is asymmetrically localized to the budding GMC and excluded from the neuroblast. After cytokinesis, prospero is translocated from the GMC cortex into the nucleus. Asymmetric cortical localization of prospero in neuroblasts requires entry into mitosis; it does not depend on numb function. prospero is also observed in cortical crescents in dividing precursors of the peripheral nervous system and adult midgut. The asymmetric cortical localization of prospero at mitosis is a mechanism for rapidly establishing distinct sibling cell fates in the CNS and possibly other tissues.

scholarly journals Antibodies from combinatorial libraries use functional receptor pleiotropism to regulate cell fates

2015 ◽  
Vol 48 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Richard A. Lerner ◽  
Rajesh K. Grover ◽  
Hongkai Zhang ◽  
Jia Xie ◽  
Kyung Ho Han ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Fate ◽  
Combinatorial Libraries ◽  
Animal Cells ◽  
Cell Fates ◽  
New Methods ◽  
A Cell ◽  
Functional Receptor

AbstractTo date, most antibodies from combinatorial libraries have been selected purely on the basis of binding. However, new methods now allow selection on the basis of function in animal cells. These selected agonist antibodies have given new insights into the important problem of signal transduction. Remarkably, when some antibodies bind to a given receptor they induce a cell fate that is different than that induced by the natural agonist to the same receptor. The fact that receptors can be functionally pleiotropic may yield new insights into the important problem of signal transduction.

scholarly journals Timing of gene expression in a cell‐fate decision system

2018 ◽  
Vol 14 (4) ◽  
Author(s):  
Delphine Aymoz ◽  
Carme Solé ◽  
Jean‐Jerrold Pierre ◽  
Marta Schmitt ◽  
Eulàlia de Nadal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Cell Fate Decision ◽  
Decision System ◽  
A Cell ◽  
Fate Decision

scholarly journals Type 1 Deiodinase Regulates ApoA-I Gene Expression and ApoA-I Synthesis Independent of Thyroid Hormone Signaling

2016 ◽  
Vol 36 (7) ◽  
pp. 1356-1366 ◽  
Author(s):  
Jing Liu ◽  
Antonio Hernandez-Ono ◽  
Mark J. Graham ◽  
Valerie Anne Galton ◽  
Henry N. Ginsberg
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Hormone Signaling ◽  
I Gene

Regulation of the uncoupling protein gene expression

1997 ◽  
Vol 136 (3) ◽  
pp. 251-264 ◽  
Author(s):  
J Enrique Silva ◽  
Rogerio Rabelo
Keyword(s):  
Gene Expression ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Uncoupling Protein ◽  
Regulatory Element ◽  
Gene Encoding ◽  
Response Elements ◽  
Brown Adipose ◽  
A Cell

Abstract Uncoupling protein (UCP) is essential to the thermogenic function of brown adipose tissue (BAT). The thermogenic role of this protein is due to its capacity to uncouple oxidative phosphorylation in a regulated manner. The thermogenic potential of BAT is determined by its content of UCP. The gene encoding this protein is under complex regulation. Catecholamines, via cAMP, thyroid hormone and retinoic acid, directly stimulate the gene acting upon an upstream (−2·28/−2·49 kb) enhancer sequence, but cAMP may act upon other sequences of the gene as well. CCAAT enhancer binding proteins and peroxisome proliferation activator receptor (PPAR)γ2 have also been implicated in the regulation of the gene acting on discrete sequences. While the thyroid hormone response and retinoic acid response elements (TRE and RARE) have been well defined, the cAMP response elements (CRE) remain elusive. The two TREs are 27 bp apart between −2·33 kb and −2·39 kb. The synergism between cAMP and thyroid hormone seems to reside in a 39 bp sequence downstream (−2·28/−2·32 kb). The most important CRE, the RARE, a cell-specific enhancer and a putative PPAR element are all concentrated in a 90 bp regulatory element of great complexity (−2·40/−22·49 kb). Other hormones, such as insulin and glucocorticoids, and IGF-I also modulate the expression of the gene but their effects seem to be largely indirect. Understanding the regulation of the UCP gene expression may facilitate the development of interventions in obesity and related disorders. European Journal of Endocrinology 136 251–264

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