Design principles of stripe-forming motifs: the role of positive feedback.
Interpreting a morphogen gradient into a single stripe of gene-expression is a fundamental unit of patterning in early embryogenesis. From both experimental data and computational studies the feed-forward motifs stand out as minimal networks capable of this patterning function. Positive feedback within gene networks has been hypothesised to enhance the sharpness and precision of gene-expression borders, however a systematic analysis has not yet been reported. Here we set out to assess this hypothesis, and find an unexpected result. The addition of positive-feedback can have different effects on two different designs of feed-forward motif- it increases the parametric robustness of one design, while being neutral or detrimental to the other. These results shed light on the abundance of the former motif and especially of mutual-inhibition positive feedback in developmental networks.
1] EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain.
Andreea
A
Munteanu
1] EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain.
James
J
Cotterell
1] Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain [2] Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA [3] Institució Catalana de Recerca i Estudis Avancats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain.
Ricard V
RV
Solé
1] EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, Spain [2] Universitat Pompeu Fabra (UPF), Dr. Aiguader 88, 08003 Barcelona, Spain [3] Institució Catalana de Recerca i Estudis Avancats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain.
James
J
Sharpe
D047108:Embryonic Development / Q000235:genetics* / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects; D018507:Gene Expression Regulation, Developmental / Q000235:genetics* / Q000502:physiology; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology