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BMC Syst Biol January 8, 2014; 8 3.

Inference of the Xenopus tropicalis embryonic regulatory network and spatial gene expression patterns.

Zheng Z , Christley S , Chiu WT , Blitz IL , Xie X , Cho KW , Nie Q .

During embryogenesis, signaling molecules produced by one cell population direct gene regulatory changes in neighboring cells and influence their developmental fates and spatial organization. One of the earliest events in the development of the vertebrate embryo is the establishment of three germ layers, consisting of the ectoderm, mesoderm and endoderm. Attempts to measure gene expression in vivo in different germ layers and cell types are typically complicated by the heterogeneity of cell types within biological samples (i.e., embryos), as the responses of individual cell types are intermingled into an aggregate observation of heterogeneous cell types. Here, we propose a novel method to elucidate gene regulatory circuits from these aggregate measurements in embryos of the frog Xenopus tropicalis using gene network inference algorithms and then test the ability of the inferred networks to predict spatial gene expression patterns. We use two inference models with different underlying assumptions that incorporate existing network information, an ODE model for steady-state data and a Markov model for time series data, and contrast the performance of the two models. We apply our method to both control and knockdown embryos at multiple time points to reconstruct the core mesoderm and endoderm regulatory circuits. Those inferred networks are then used in combination with known dorsal-ventral spatial expression patterns of a subset of genes to predict spatial expression patterns for other genes. Both models are able to predict spatial expression patterns for some of the core mesoderm and endoderm genes, but interestingly of different gene subsets, suggesting that neither model is sufficient to recapitulate all of the spatial patterns, yet they are complementary for the patterns that they do capture. The presented methodology of gene network inference combined with spatial pattern prediction provides an additional layer of validation to elucidate the regulatory circuits controlling the spatial-temporal dynamics in embryonic development.

PubMed ID: 24397936
PMC ID: PMC3896677
Article link: BMC Syst Biol
Grant support: [+]
Genes referenced: bix1.1 bix1.2 bix1.3 bmp4 ctnnb1 foxa1 foxa2 foxa4 foxh1 foxh1.2 frzb gata4 gata5 gata6 gsc hhex hnf1b lhx1 mespb mix1 mixer msx1 myc myf5 myod1 nodal3.1 nodal3.2 nodal6 otx2 sox17a sox17b.1 sox21 sox7 tbxt vegt ventx1.2 ventx2.2 wnt11

Article Images: [+] show captions
References [+] :
Bansal, How to infer gene networks from expression profiles. 2007, Pubmed

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