RRC ID |
30647
|
著者 |
Ji N, Middelkoop TC, Mentink RA, Betist MC, Tonegawa S, Mooijman D, Korswagen HC, van Oudenaarden A.
|
タイトル |
Feedback control of gene expression variability in the Caenorhabditis elegans Wnt pathway.
|
ジャーナル |
Cell
|
Abstract |
Variability in gene expression contributes to phenotypic heterogeneity even in isogenic populations. Here, we used the stereotyped, Wnt signaling-dependent development of the Caenorhabditis elegans Q neuroblast to probe endogenous mechanisms that control gene expression variability. We found that the key Hox gene that orients Q neuroblast migration exhibits increased gene expression variability in mutants in which Wnt pathway activity has been perturbed. Distinct features of the gene expression distributions prompted us on a systematic search for regulatory interactions, revealing a network of interlocked positive and negative feedback loops. Interestingly, positive feedback appeared to cooperate with negative feedback to reduce variability while keeping the Hox gene expression at elevated levels. A minimal model correctly predicts the increased gene expression variability across mutants. Our results highlight the influence of gene network architecture on expression variability and implicate feedback regulation as an effective mechanism to ensure developmental robustness.
|
巻・号 |
155(4)
|
ページ |
869-80
|
公開日 |
2013-11-7
|
DOI |
10.1016/j.cell.2013.09.060
|
PII |
S0092-8674(13)01279-8
|
PMID |
24209624
|
MeSH |
Animals
Caenorhabditis elegans / cytology
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics
Cell Movement
Embryo, Nonmammalian / cytology
Embryo, Nonmammalian / metabolism
Feedback, Physiological
Frizzled Receptors / genetics
Frizzled Receptors / metabolism
Gene Regulatory Networks
Genetic Variation*
Glycoproteins / genetics
Homeodomain Proteins / genetics
Transcription Factors / genetics
Wnt Proteins
Wnt Signaling Pathway*
|
IF |
38.637
|
引用数 |
50
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
線虫 |
tm1320 |