scholarly journals Stochasticity and determinism in cell fate decisions

Development ◽  
2020 ◽  
Vol 147 (14) ◽  
pp. dev181495 ◽  
Author(s):  
Christoph Zechner ◽  
Elisa Nerli ◽  
Caren Norden
Keyword(s):  
Cell Fate ◽  
Neuronal Cell ◽  
Cell Fate Decisions ◽  
Over Time

ABSTRACTDuring development, cells need to make decisions about their fate in order to ensure that the correct numbers and types of cells are established at the correct time and place in the embryo. Such cell fate decisions are often classified as deterministic or stochastic. However, although these terms are clearly defined in a mathematical sense, they are sometimes used ambiguously in biological contexts. Here, we provide some suggestions on how to clarify the definitions and usage of the terms stochastic and deterministic in biological experiments. We discuss the frameworks within which such clear definitions make sense and highlight when certain ambiguity prevails. As an example, we examine how these terms are used in studies of neuronal cell fate decisions and point out areas in which definitions and interpretations have changed and matured over time. We hope that this Review will provide some clarification and inspire discussion on the use of terminology in relation to fate decisions.

Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development

Development ◽  
1992 ◽  
Vol 115 (3) ◽  
pp. 737-744 ◽  
Author(s):  
F.F. Del Amo ◽  
D.E. Smith ◽  
P.J. Swiatek ◽  
M. Gendron-Maguire ◽  
R.J. Greenspan ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mouse Embryo ◽  
Transmembrane Protein ◽  
Neuronal Cell ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Mouse Development ◽  
Cell Fate Decisions ◽  
Early Mouse ◽  
Partial Cdna Clone

The Notch gene of Drosophila encodes a large transmembrane protein involved in cell-cell interactions and cell fate decisions in the Drosophila embryo. To determine if a gene homologous to Drosophila Notch plays a role in early mouse development, we screened a mouse embryo cDNA library with probes from the Xenopus Notch homolog, Xotch. A partial cDNA clone encoding the mouse Notch homolog, which we have termed Motch, was used to analyze expression of the Motch gene. Motch transcripts were detected in a wide variety of adult tissues, which included derivatives of all three germ layers. Differentiation of P19 embryonal carcinoma cells into neuronal cell types resulted in increased expression of Motch RNA. In the postimplantation mouse embryo Motch transcripts were first detected in mesoderm at 7.5 days post coitum (dpc). By 8.5 dpc, transcript levels were highest in presomitic mesoderm, mesenchyme and endothelial cells, while much lower levels were detected in neuroepithelium. In contrast, at 9.5 dpc, neuroepithelium was a major site of Motch expression. Transcripts were also abundant in cell types derived from neural crest. These data suggest that the Motch gene plays multiple roles in patterning and differentiation of the early postimplantation mouse embryo.

scholarly journals The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders

2018 ◽  
Author(s):  
Cheen Euong Ang ◽  
Qing Ma ◽  
Orly L. Wapinski ◽  
Shenghua Fan ◽  
Ryan A. Flynn ◽  
...  
Keyword(s):  
Cell Fate ◽  
Human Genetics ◽  
Neuronal Cell ◽  
Chromosomal Translocation ◽  
Autism Spectrum ◽  
Cell Fate Decisions ◽  
Number Variation ◽  
Neuronal Genes ◽  
Neuronal Lineage ◽  
Candidate Loci

AbstractLong noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically lnc-NR2F1. We further show that lnc-NR2F1 is an evolutionarily conserved lncRNA functionally enhances induced neuronal cell maturation and directly occupies and regulates transcription of neuronal genes including autism-associated genes. Thus, integrating human genetics and functional testing in neuronal lineage induction is a promising approach for discovering candidate lncRNAs involved in neurodevelopmental diseases.

scholarly journals The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Cheen Euong Ang ◽  
Qing Ma ◽  
Orly L Wapinski ◽  
ShengHua Fan ◽  
Ryan A Flynn ◽  
...  
Keyword(s):  
Cell Fate ◽  
Human Genetics ◽  
Neuronal Cell ◽  
Chromosomal Translocation ◽  
Autism Spectrum ◽  
Cell Fate Decisions ◽  
Number Variation ◽  
Neuronal Genes ◽  
Neuronal Lineage ◽  
Candidate Loci

Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically lnc-NR2F1. We further show that lnc-NR2F1 is an evolutionarily conserved lncRNA functionally enhances induced neuronal cell maturation and directly occupies and regulates transcription of neuronal genes including autism-associated genes. Thus, integrating human genetics and functional testing in neuronal lineage induction is a promising approach for discovering candidate lncRNAs involved in neurodevelopmental diseases.

scholarly journals Neuronal cell fate decisions

Worm ◽  
2013 ◽  
Vol 2 (4) ◽  
pp. e27284 ◽  
Author(s):  
Jakob Gramstrup Petersen ◽  
Roger Pocock
Keyword(s):  
Cell Fate ◽  
Neuronal Cell ◽  
Cell Fate Decisions

scholarly journals Reliable cell cycle commitment in budding yeast is ensured by signal integration

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Xili Liu ◽  
Xin Wang ◽  
Xiaojing Yang ◽  
Sen Liu ◽  
Lingli Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Decision Making ◽  
Cell Fate ◽  
Kinase Activity ◽  
Budding Yeast ◽  
Time Integration ◽  
Cellular Level ◽  
Signal Integration ◽  
Cell Fate Decisions ◽  
Over Time

Cell fate decisions are critical for life, yet little is known about how their reliability is achieved when signals are noisy and fluctuating with time. In this study, we show that in budding yeast, the decision of cell cycle commitment (Start) is determined by the time integration of its triggering signal Cln3. We further identify the Start repressor, Whi5, as the integrator. The instantaneous kinase activity of Cln3-Cdk1 is recorded over time on the phosphorylated Whi5, and the decision is made only when phosphorylated Whi5 reaches a threshold. Cells adjust the threshold by modulating Whi5 concentration in different nutrient conditions to coordinate growth and division. Our work shows that the strategy of signal integration, which was previously found in decision-making behaviors of animals, is adopted at the cellular level to reduce noise and minimize uncertainty.

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