scholarly journals Evolution of abbreviated development in Heliocidaris erythrogramma dramatically re-wired the highly conserved sea urchin developmental gene regulatory network to decouple signaling center function from ultimate fate

2019 ◽  
Author(s):  
Allison Edgar ◽  
Maria Byrne ◽  
David R. McClay ◽  
Gregory A. Wray
Keyword(s):  
Early Development ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Sea Urchins ◽  
Stabilizing Selection ◽  
Developmental Gene ◽  
Heliocidaris Erythrogramma ◽  
Signaling Center ◽  
Gene Regulatory ◽  
Ultimate Fate

AbstractDevelopmental gene regulatory networks (GRNs) describe the interactions among gene products that drive the differential transcriptional and cell regulatory states that pattern the embryo and specify distinct cell fates. GRNs are often deeply conserved, but whether this is the product of constraint inherent to the network structure or stabilizing selection remains unclear. We have constructed the first formal GRN for early development in Heliocidaris erythrogramma, a species with dramatically accelerated, direct development. This life history switch has important ecological consequences, arose rapidly, and has evolved independently many times in echinoderms, suggesting it is a product of selection. We find that H. erythrogramma exhibits dramatic differences in GRN topology compared with ancestral, indirect-developing sea urchins. In particular, the GRN sub-circuit that directs the early and autonomous commitment of skeletogenic cell precursors in indirect developers appears to be absent in H. erythrogramma, a particularly striking change in relation to both the prior conservation of this sub-circuit and the key role that these cells play ancestrally in early development as the embryonic signaling center. These results show that even highly conserved molecular mechanisms of early development can be substantially reconfigured in a relatively short evolutionary time span, suggesting that selection rather than constraint is responsible for the striking conservation of the GRN among other sea urchins.

scholarly journals Divergence of gene regulatory network linkages during specification of ectoderm and mesoderm in early development of sea urchins

2016 ◽  
Author(s):  
Eric M. Erkenbrack ◽  
Eric H. Davidson
Keyword(s):  
Early Development ◽  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Sea Urchins ◽  
Regulatory Genes ◽  
Geological Time ◽  
Appreciable Change ◽  
Comparative Analyses ◽  
Temporal Gene Expression ◽  
Gene Regulatory

AbstractDevelopmental gene regulatory networks (GRNs) are assemblages of gene regulatory interactions that direct ontogeny of animal body plans. Studies of GRNs operating in early development of euechinoid sea urchins has revealed that little appreciable change has occurred since their divergence approximately 90 million years ago (mya). These observations suggest that strong conservation of GRN architecture has been maintained in early development of the sea urchin lineage. To test whether this is true for all sea urchins, comparative analyses of echinoid taxa that diverged deeper in geological time must be conducted. Recent studies highlighted extensive divergence of skeletogenic mesoderm specification in the sister clade of euechinoids, the cidaroids, suggesting that comparative analyses of cidaroid GRN architecture may confer a greater understanding of the evolutionary dynamics of developmental GRNs. Here, we report spatiotemporal patterning of 55 regulatory genes and perturbation analyses of key regulatory genes involved in euechinoid oral-aboral patterning of non-skeletogenic mesodermal and ectodermal domains in early development of the cidaroid Eucidaris tribuloides. Our results indicate that developmental GRNs directing mesodermal and ectodermal specification have undergone marked alterations since the divergence of cidaroids and euechinoids. Notably, statistical and clustering analyses of echinoid temporal gene expression datasets indicate that regulation of mesodermal genes has diverged more markedly than regulation of ectodermal genes. Although research on indirect-developing euechinoid sea urchins suggests strong conservation of GRN circuitry during early embryogenesis, this study indicates that since the divergence of cidaroids and euechinoids developmental GRNs have undergone significant divergence.

scholarly journals Divergence of ectodermal and mesodermal gene regulatory network linkages in early development of sea urchins

2016 ◽  
Vol 113 (46) ◽  
pp. E7202-E7211 ◽  
Author(s):  
Eric M. Erkenbrack
Keyword(s):  
Early Development ◽  
Regulatory Networks ◽  
Evolutionary Dynamics ◽  
Sea Urchins ◽  
Regulatory Genes ◽  
Geological Time ◽  
Appreciable Change ◽  
Comparative Analyses ◽  
Temporal Gene Expression ◽  
Gene Regulatory

Developmental gene regulatory networks (GRNs) are assemblages of gene regulatory interactions that direct ontogeny of animal body plans. Studies of GRNs operating in the early development of euechinoid sea urchins have revealed that little appreciable change has occurred since their divergence ∼90 million years ago (mya). These observations suggest that strong conservation of GRN architecture was maintained in early development of the sea urchin lineage. Testing whether this holds for all sea urchins necessitates comparative analyses of echinoid taxa that diverged deeper in geological time. Recent studies highlighted extensive divergence of skeletogenic mesoderm specification in the sister clade of euechinoids, the cidaroids, suggesting that comparative analyses of cidaroid GRN architecture may confer a greater understanding of the evolutionary dynamics of developmental GRNs. Here I report spatiotemporal patterning of 55 regulatory genes and perturbation analyses of key regulatory genes involved in euechinoid oral–aboral patterning of nonskeletogenic mesodermal and ectodermal domains in early development of the cidaroid Eucidaris tribuloides. These results indicate that developmental GRNs directing mesodermal and ectodermal specification have undergone marked alterations since the divergence of cidaroids and euechinoids. Notably, statistical and clustering analyses of echinoid temporal gene expression datasets indicate that regulation of mesodermal genes has diverged more markedly than regulation of ectodermal genes. Although research on indirect-developing euechinoid sea urchins suggests strong conservation of GRN circuitry during early embryogenesis, this study indicates that since the divergence of cidaroids and euechinoids, developmental GRNs have undergone significant, cell type–biased alterations.

scholarly journals Mapping the Germline and Somatic Mutation Interaction Landscape in Indolent and Aggressive Prostate Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Tarun Karthik Kumar Mamidi ◽  
Jiande Wu ◽  
Chindo Hicks
Keyword(s):  
Signaling Pathways ◽  
Somatic Mutation ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Somatic Mutations ◽  
Multiple Gene ◽  
Gene Regulatory ◽  
Aggressive Tumors ◽  
Prostate Cancers ◽  
Mutation Information

Background. A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment. However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal. PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis. However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized. The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa. Materials and Methods. We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes. Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis. Results. We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa. We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa. Conclusion. The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa. The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations. Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.

scholarly journals Comprehensive Assessment and Network Analysis of the Emerging Genetic Susceptibility Landscape of Prostate Cancer

2013 ◽  
Vol 12 ◽  
pp. CIN.S12128 ◽  
Author(s):  
Chindo Hicks ◽  
Lucio Miele ◽  
Tejaswi Koganti ◽  
Srinivasan Vijayakumar
Keyword(s):  
Prostate Cancer ◽  
Genetic Susceptibility ◽  
Pathway Analysis ◽  
Gene Regulatory Networks ◽  
Genetic Variants ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Comprehensive Assessment ◽  
Increased Risk ◽  
Gene Regulatory

Background Recent advances in high-throughput genotyping have made possible identification of genetic variants associated with increased risk of developing prostate cancer using genome-wide associations studies (GWAS). However, the broader context in which the identified genetic variants operate is poorly understood. Here we present a comprehensive assessment, network, and pathway analysis of the emerging genetic susceptibility landscape of prostate cancer. Methods We created a comprehensive catalog of genetic variants and associated genes by mining published reports and accompanying websites hosting supplementary data on GWAS. We then performed network and pathway analysis using single nucleotide polymorphism (SNP)-containing genes to identify gene regulatory networks and pathways enriched for genetic variants. Results We identified multiple gene networks and pathways enriched for genetic variants including IGF-1, androgen biosynthesis and androgen signaling pathways, and the molecular mechanisms of cancer. The results provide putative functional bridges between GWAS findings and gene regulatory networks and biological pathways.

scholarly journals Hub genes with positive feedbacks function as master switches in developmental gene regulatory networks

2009 ◽  
Vol 25 (15) ◽  
pp. 1898-1904 ◽  
Author(s):  
Chang H. Seo ◽  
Jeong-Rae Kim ◽  
Man-Sun Kim ◽  
Kwang-Hyun Cho
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Developmental Gene ◽  
Hub Genes ◽  
Positive Feedbacks ◽  
Gene Regulatory

Developmental gene regulatory networks in the zebrafish embryo

2009 ◽  
Vol 1789 (4) ◽  
pp. 279-298 ◽  
Author(s):  
Tzu-Min Chan ◽  
William Longabaugh ◽  
Hamid Bolouri ◽  
Hua-Ling Chen ◽  
Wen-Fang Tseng ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Zebrafish Embryo ◽  
Developmental Gene ◽  
Gene Regulatory
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