scholarly journals Interdependent regulation of stereotyped and stochastic photoreceptor fates in the fly eye

2019 ◽  
Author(s):  
Adam C. Miller ◽  
Elizabeth Urban ◽  
Eric L. Lyons ◽  
Tory G. Herman ◽  
Robert J. Johnston
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Gene Networks ◽  
Control Cell ◽  
Regulatory Mechanisms ◽  
Cell Fates ◽  
Feedback Mechanisms ◽  
Fate Specification ◽  
Gene Regulatory ◽  
Fly Eye

AbstractDiversification of neuronal subtypes often requires stochastic gene regulatory mechanisms. How stochastically expressed transcription factors interact with other regulators in gene networks to specify cell fates is poorly understood. The random mosaic of color-detecting R7 photoreceptor subtypes in Drosophila is controlled by the stochastic on/off expression of the transcription factor Spineless (Ss). In SsON R7s, Ss induces expression of Rhodopsin 4 (Rh4), whereas in SsOFF R7s, the absence of Ss allows expression of Rhodopsin 3 (Rh3). Here, we find that the transcription factor Runt, which is initially expressed in all R7s, activates expression of Spineless in a random subset of R7s. Later, as R7s develop, Ss negatively feeds back onto Runt to prevent repression of Rh4 and ensure proper fate specification. Together, stereotyped and stochastic regulatory inputs are integrated into feedforward and feedback mechanisms to control cell fate.

scholarly journals Calpain DEK1 acts as a developmental switch gatekeeping cell fate transitions

2021 ◽  
Author(s):  
Viktor Demko ◽  
Tatiana Belova ◽  
Maxim Messerer ◽  
Torgeir R. Hvidsten ◽  
Pierre-François Perroud ◽  
...  
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Data Science ◽  
Control Cell ◽  
Cysteine Proteases ◽  
Regulatory Role ◽  
Phenotypic Traits ◽  
Cell Fates ◽  
Gene Regulatory ◽  
Developmental Switch

SummaryCalpains are cysteine proteases that control cell fate transitions. Although calpains are viewed as modulatory proteases displaying severe, pleiotropic phenotypes in eukaryotes, human calpain targets are also directed to the N-end rule degradatory pathway. Several of these destabilized targets are transcription factors, hinting at a gene regulatory role. Here, we analyze the gene regulatory networks of Physcomitrium patens and characterize the regulons that are deregulated in DEK1 calpain mutants. Predicted cleavage patterns of regulatory hierarchies in the five DEK1-controlled subnetworks are consistent with the gene’s pleiotropy and the regulatory role in cell fate transitions targeting a broad spectrum of functions. Network structure suggests DEK1-gated sequential transition between cell fates in 2D to 3D development. We anticipate that both our method combining phenotyping, transcriptomics and data science to dissect phenotypic traits and our model explaining the calpain’s role as a switch gatekeeping cell fate transitions will inform biology beyond plant development.

scholarly journals Context-dependent roles of YAP/TAZ in stem cell fates and cancer

2021 ◽  
Author(s):  
Lucy LeBlanc ◽  
Nereida Ramirez ◽  
Jonghwan Kim
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Control Cell ◽  
Substantial Portion ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Cell Death Pathways ◽  
Multiple Context ◽  
Cancer Cell Survival ◽  
Context Dependent

AbstractHippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.

scholarly journals Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating the Shh signaling response

Development ◽  
2020 ◽  
Vol 147 (16) ◽  
pp. dev191023 ◽  
Author(s):  
Kayt Scott ◽  
Rebecca O'Rourke ◽  
Austin Gillen ◽  
Bruce Appel
Keyword(s):  
Motor Neuron ◽  
Cell Fate ◽  
Motor Neurons ◽  
Oligodendrocyte Precursor Cells ◽  
Cell Fate Specification ◽  
Cell Fates ◽  
Shh Signaling ◽  
Fate Specification ◽  
The People ◽  
Oligodendrocyte Precursor

ABSTRACTSpinal cord pMN progenitors sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Some OPCs differentiate rapidly as myelinating oligodendrocytes, whereas others remain into adulthood. How pMN progenitors switch from producing motor neurons to OPCs with distinct fates is poorly understood. pMN progenitors express prdm8, which encodes a transcriptional repressor, during motor neuron and OPC formation. To determine whether prdm8 controls pMN cell fate specification, we used zebrafish as a model system to investigate prdm8 function. Our analysis revealed that prdm8 mutant embryos have fewer motor neurons resulting from a premature switch from motor neuron to OPC production. Additionally, prdm8 mutant larvae have excess oligodendrocytes and a concomitant deficit of OPCs. Notably, pMN cells of mutant embryos have elevated Shh signaling, coincident with the motor neuron to OPC switch. Inhibition of Shh signaling restored the number of motor neurons to normal but did not rescue the proportion of oligodendrocytes. These data suggest that Prdm8 regulates the motor neuron-OPC switch by controlling the level of Shh activity in pMN progenitors, and also regulates the allocation of oligodendrocyte lineage cell fates.This article has an associated ‘The people behind the papers’ interview.

scholarly journals Developmental clock and mechanism of de novo polarization of the mouse embryo

Science ◽  
2020 ◽  
Vol 370 (6522) ◽  
pp. eabd2703
Author(s):  
Meng Zhu ◽  
Jake Cornwall-Scoones ◽  
Peizhe Wang ◽  
Charlotte E. Handford ◽  
Jie Na ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
De Novo ◽  
Cell Fate Specification ◽  
Mouse Development ◽  
Fate Specification ◽  
Apical Domain ◽  
Transcription Factor 4 ◽  
Genome Activation ◽  
Zygotic Genome

Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.

scholarly journals FOXO transcription factor family in cancer and metastasis

2020 ◽  
Vol 39 (3) ◽  
pp. 681-709 ◽  
Author(s):  
Yannasittha Jiramongkol ◽  
Eric W.-F. Lam
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Gene Networks ◽  
Cancer Metastasis ◽  
Metabolic Diseases ◽  
Genetic Disorders ◽  
Primary Tumour ◽  
Control Cell ◽  
Normal Tissues ◽  
Foxo Transcription Factors

Abstract Forkhead box O (FOXO) transcription factors regulate diverse biological processes, affecting development, metabolism, stem cell maintenance and longevity. They have also been increasingly recognised as tumour suppressors through their ability to regulate genes essential for cell proliferation, cell death, senescence, angiogenesis, cell migration and metastasis. Mechanistically, FOXO proteins serve as key connection points to allow diverse proliferative, nutrient and stress signals to converge and integrate with distinct gene networks to control cell fate, metabolism and cancer development. In consequence, deregulation of FOXO expression and function can promote genetic disorders, metabolic diseases, deregulated ageing and cancer. Metastasis is the process by which cancer cells spread from the primary tumour often via the bloodstream or the lymphatic system and is the major cause of cancer death. The regulation and deregulation of FOXO transcription factors occur predominantly at the post-transcriptional and post-translational levels mediated by regulatory non-coding RNAs, their interactions with other protein partners and co-factors and a combination of post-translational modifications (PTMs), including phosphorylation, acetylation, methylation and ubiquitination. This review discusses the role and regulation of FOXO proteins in tumour initiation and progression, with a particular emphasis on cancer metastasis. An understanding of how signalling networks integrate with the FOXO transcription factors to modulate their developmental, metabolic and tumour-suppressive functions in normal tissues and in cancer will offer a new perspective on tumorigenesis and metastasis, and open up therapeutic opportunities for malignant diseases.

Stem Cell Fate Specification: Role of Master Regulatory Switch Transcription Factor PU.1 in Differential Hematopoiesis

2005 ◽  
Vol 14 (2) ◽  
pp. 140-152 ◽  
Author(s):  
Gurudutta U. Gangenahalli ◽  
Pallavi Gupta ◽  
Daman Saluja ◽  
Yogesh K. Verma ◽  
Vimal Kishore ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Fate Specification ◽  
Stem Cell Fate ◽  
Fate Specification

scholarly journals Focal adhesion kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate

2011 ◽  
Vol 22 (13) ◽  
pp. 2409-2421 ◽  
Author(s):  
Yuri Fonar ◽  
Yoni E. Gutkovich ◽  
Heather Root ◽  
Anastasia Malyarova ◽  
Emil Aamar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Focal Adhesion Kinase ◽  
Cell Fate ◽  
Focal Adhesion ◽  
Control Cell ◽  
Focal Adhesions ◽  
Neural Plate ◽  
Cell Fate Specification ◽  
Fate Specification

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase protein localized to regions called focal adhesions, which are contact points between cells and the extracellular matrix. FAK protein acts as a scaffold to transfer adhesion-dependent and growth factor signals into the cell. Increased FAK expression is linked to aggressive metastatic and invasive tumors. However, little is known about its normal embryonic function. FAK protein knockdown during early Xenopus laevis development anteriorizes the embryo. Morphant embryos express increased levels of anterior neural markers, with reciprocally reduced posterior neural marker expression. Posterior neural plate folding and convergence-extension is also inhibited. This anteriorized phenotype resembles that of embryos knocked down zygotically for canonical Wnt signaling. FAK and Wnt3a genes are both expressed in the neural plate, and Wnt3a expression is FAK dependent. Ectopic Wnt expression rescues this FAK morphant anteriorized phenotype. Wnt3a thus acts downstream of FAK to balance anterior–posterior cell fate specification in the developing neural plate. Wnt3a gene expression is also FAK dependent in human breast cancer cells, suggesting that this FAK–Wnt linkage is highly conserved. This unique observation connects the FAK- and Wnt-signaling pathways, both of which act to promote cancer when aberrantly activated in mammalian cells.

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