当前位置： SCI文献检索 > GENETICS期刊下所有文献 > Modeling the zebrafish segmentation clock's gene regulatory network constrained by expression data suggests evolutionary transitions between oscillating and nonoscillating transcription.

Modeling the zebrafish segmentation clock's gene regulatory network constrained by expression data suggests evolutionary transitions between oscillating and nonoscillating transcription.

Abstract：

:During segmentation of vertebrate embryos, somites form in accordance with a periodic pattern established by the segmentation clock. In the zebrafish (Danio rerio), the segmentation clock includes six hairy/enhancer of split-related (her/hes) genes, five of which oscillate due to negative autofeedback. The nonoscillating gene hes6 forms the hub of a network of 10 Her/Hes protein dimers, which includes 7 DNA-binding dimers and 4 weak or non-DNA-binding dimers. The balance of dimer species is critical for segmentation clock function, and loss-of-function studies suggest that the her genes have both unique and redundant functions within the clock. However, the precise regulatory interactions underlying the negative feedback loop are unknown. Here, we combine quantitative experimental data, in silico modeling, and a global optimization algorithm to identify a gene regulatory network (GRN) designed to fit measured transcriptional responses to gene knockdown. Surprisingly, we find that hes6, the clock gene that does not oscillate, responds to negative feedback. Consistent with prior in silico analyses, we find that variation in transcription, translation, and degradation rates can mediate the gain and loss of oscillatory behavior for genes regulated by negative feedback. Extending our study, we found that transcription of the nonoscillating Fgf pathway gene sef responds to her/hes perturbation similarly to oscillating her genes. These observations suggest a more extensive underlying regulatory similarity between the zebrafish segmentation clock and the mouse and chick segmentation clocks, which exhibit oscillations of her/hes genes as well as numerous other Notch, Fgf, and Wnt pathway genes.

journal_name

Genetics

journal_title

Genetics

authors

Schwendinger-Schreck J,Kang Y,Holley SA

doi

10.1534/genetics.114.163642

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

725-38

issue

eissn

0016-6731

issn

1943-2631

pii

genetics.114.163642

journal_volume

197

pub_type

杂志文章

在线工具

Modeling the zebrafish segmentation clock's gene regulatory network constrained by expression data suggests evolutionary transitions between oscillating and nonoscillating transcription.