Self-enhanced ligand degradation underlies robustness of morphogen gradients.
Morphogen gradients provide long-range positional information by extending across a developing field. To ensure reproducible patterning, their profile is invariable despite genetic or environmental fluctuations. Common models assume a morphogen profile that decays exponentially. Here, we show that exponential profiles cannot, at the same time, buffer fluctuations in morphogen production rate and define long-range gradients. To comply with both requirements, morphogens should decay rapidly close to their source but at a significantly slower rate over most of the field. Numerical search revealed two network designs that support robustness to fluctuations in morphogen production rate. In both cases, morphogens enhance their own degradation, leading to a higher degradation rate close to their source. This is achieved through reciprocal interactions between the morphogen and its receptor. The two robust networks are consistent with properties of the Wg and Hh morphogens in the Drosophila wing disc and provide novel insights into their function.
Eldar
Avigdor
A
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Rosin
Dalia
D
Shilo
Ben-Zion
BZ
Barkai
Naama
N
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D003198:Computer Simulation; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D008024:Ligands; D008164:Luminescent Proteins / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis / Q000235:genetics* / Q000502:physiology; D016571:Neural Networks, Computer; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014018:Tissue Distribution; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D008024:Ligands; D008164:Luminescent Proteins; D011518:Proto-Oncogene Proteins; D051155:Wnt1 Protein; C074622:wg protein, Drosophila; D049452:Green Fluorescent Proteins; C077245:hh protein, Drosophila