A model of the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva

Weinstein, Nathan; Ortiz-Gutiérrez, Elizabeth; Muñoz, Stalin; Rosenblueth, David A.; Álvarez-Buylla, Elena; Mendoza, Luis

doi:10.1186/s12859-015-0498-z

Cited by 9 publications

(11 citation statements)

References 130 publications

(114 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Each of these networks can attain any of several stable gene activity phenotypes (GAPs), as they participate in developmental decisions in plants and animals ( Table 1 ). The sample contains studies in plants [ 64 – 66 ], insects [ 67 ], nematodes [ 68 ], echinoderms [ 69 ] and mammals [ 70 – 75 ]. The networks vary greatly in size (ranging from 5 to 94 nodes) and number of interactions (13-209).…”

Section: Resultsmentioning

confidence: 99%

On the role of sparseness in the evolution of modularity in gene regulatory networks

Espinosa‐Soto

2018

PLoS Comput Biol

View full text Add to dashboard Cite

Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

show abstract

Section: Resultsmentioning

confidence: 99%

On the role of sparseness in the evolution of modularity in gene regulatory networks

Espinosa‐Soto

2018

PLoS Comput Biol

View full text Add to dashboard Cite

show abstract

“…These states include the attractor itself. In models where an attractor corresponds to just one cell type (see for example Weinstein et al (2015)), it is customary to characterize the basins of attraction. In the present model, however, a given attractor may correspond to more than one label, and vice versa, one label can be assigned to more than one attractor.…”

Section: Molecular Pattern Identificationmentioning

confidence: 99%

A Computational Model of the Endothelial to Mesenchymal Transition

2020

Self Cite

View full text Add to dashboard Cite

Endothelial cells (ECs) form the lining of lymph and blood vessels. Changes in tissue requirements or wounds may cause ECs to behave as tip or stalk cells. Alternatively, they may differentiate into mesenchymal cells (MCs). These processes are known as EC activation and endothelial-to-mesenchymal transition (EndMT), respectively. EndMT, Tip, and Stalk EC behaviors all require SNAI1, SNAI2, and Matrix metallopeptidase (MMP) function. However, only EndMT inhibits the expression of VE-cadherin, PECAM1, and VEGFR2, and also leads to EC detachment. Physiologically, EndMT is involved in heart valve development, while a defective EndMT regulation is involved in the physiopathology of cardiovascular malformations, congenital heart disease, systemic and organ fibrosis, pulmonary arterial hypertension, and atherosclerosis. Therefore, the control of EndMT has many promising potential applications in regenerative medicine. Despite the fact that many molecular components involved in EC activation and EndMT have been characterized, the system-level molecular mechanisms involved in this process have not been elucidated. Toward this end, hereby we present Boolean network model of the molecular involved in the regulation of EC activation and EndMT. The simulated dynamic behavior of our model reaches fixed and cyclic patterns of activation that correspond to the expected EC and MC cell types and behaviors, recovering most of the specific effects of simple gain and loss-of-function mutations as well as the conditions associated with the progression of several diseases. Therefore, our model constitutes a theoretical framework that can be used to generate hypotheses and guide experimental inquiry to comprehend the regulatory mechanisms behind EndMT. Our main findings include that both the extracellular microevironment and the pattern of molecular activity within the cell regulate EndMT. EndMT requires a lack of VEGFA and sufficient oxygen in the extracellular microenvironment as well as no FLI1 and GATA2 activity within the cell. Additionally Tip cells cannot undergo EndMT directly. Furthermore, the specific conditions that are sufficient to trigger EndMT depend on the specific pattern of molecular activation within the cell.

show abstract

“…cpz-1 localizes to the developing vulva, and cpz-1 RNAi results in defective vulval morphology ( Hashmi et al 2004 ). cdk-1 regulates lin-12/Notch in a cell cycle-dependent manner ( Nusser-Stein et al 2012 ; Weinstein et al 2015 ). The remaining four genes, spp-1 , rpn-7 , his-7 , and rnr-1 had no reported function in the vulva system.…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress responses, and aging

Mallick

Jhaveri

Jeon

et al. 2021

G3 Genes|Genomes|Genetics

View full text Add to dashboard Cite

The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode Caenorhabditis elegans have shown that the Axin homolog PRY-1 plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Knocking down eight of the genes (spp-1, clsp-1, ard-1, rpn-7, cpz-1, his-7, cdk-1, and rnr-1) via RNA interference efficiently suppressed the multivulva phenotype of pry-1 mutants. In all cases, the ectopic induction of P3.p vulval precursor cell was also inhibited. The suppressor genes are members of known gene families in eukaryotes and perform essential functions. Our genetic interaction experiments revealed that in addition to their role in vulval development, these genes participate in one or more pry-1-mediated biological events. Whereas four of them (cpz-1, his-7, cdk-1, and rnr-1) function in both stress response and aging, two (spp-1 and ard-1) are specific to stress response. Altogether, these findings demonstrate the important role of pry-1 suppressors in regulating developmental and post-developmental processes in C. elegans. Given that the genes described in this study are conserved, future investigations of their interactions with Axin and their functional specificity promises to uncover the genetic network of Axin in metazoans.

show abstract

A model of the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva

Cited by 9 publications

References 130 publications

On the role of sparseness in the evolution of modularity in gene regulatory networks

On the role of sparseness in the evolution of modularity in gene regulatory networks

A Computational Model of the Endothelial to Mesenchymal Transition

Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress responses, and aging

Contact Info

Product

Resources

About