Location: Notch signaling pathway @ 07d231f0216e / Documentation_Notch.htm

Author:
Nazanin ebrahimi <nebr002@aucklanduni.ac.nz>
Date:
2014-11-04 12:38:55+13:00
Desc:
adding reST document
Permanent Source URI:
https://models.fieldml.org/workspace/1cd/rawfile/07d231f0216e57f2e4be3b1d97814febb1fc57fe/Documentation_Notch.htm

<span style="font-size:14.0pt;mso-bidi-font-size:12.0pt;mso-ascii-font-family:Calibri; mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ">Mathematical model for the Notch signalling pathway during <span class="SpellE">somitogenesis</span></span></b><span style="font-size:12.0pt;mso-bidi-font-size:11.0pt;mso-ascii-font-family:Calibri; mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ"></span></p> <p class="MsoNormal" style="text-align:justify;line-height:normal"><b><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; color:black;mso-fareast-language:EN-NZ">Model status</span></b><span style="mso-ascii-font-family:Calibri;mso-fareast-font-family:"Times New Roman"; mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri;color:black; mso-fareast-language:EN-NZ"></span></p> <p class="MsoNormal" style="text-align:justify;line-height:normal"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; color:black;mso-fareast-language:EN-NZ">This <span class="SpellE">CellML</span> model runs in both <span class="SpellE">OpenCell</span> and <span class="SpellE">OpenCOR</span> to reproduce the simulation results of the Notch signalling model from Figure 2 in the original published paper (Wang et al., 2013).</span></p> <p class="MsoNormal" style="text-align:justify;line-height:normal"><b><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; color:black;mso-fareast-language:EN-NZ">Model Structure</span></b><span style="mso-ascii-font-family:Calibri;mso-fareast-font-family:"Times New Roman"; mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri;color:black; mso-fareast-language:EN-NZ"></span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal"><b><span style="font-size:12.0pt;mso-ascii-font-family: Calibri;mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ">Abstract:</span></b></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal"><span style="font-size:12.0pt;mso-ascii-font-family: Calibri;mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ">Background: <span class="SpellE">Somitogenesis</span> is a fundamental characteristic feature of development in various animal embryos. Molecular evidence has proved that the Notch and <span class="SpellE">Wnt</span> pathways play important roles in regulating the process of <span class="SpellE">somitogenesis</span> and there is crosstalk between these two pathways. However, it is difficult to investigate the detailed mechanism of these two pathways and their interactions in <span class="SpellE">somitogenesis</span> through biological experiments. In recent years some mathematical models have been proposed for the purpose of studying the dynamics of the Notch and <span class="SpellE">Wnt</span> pathways in <span class="SpellE">somitogenesis</span>. Unfortunately, only a few of these models have explored the interactions between them.</span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal"><span style="font-size:12.0pt;mso-ascii-font-family: Calibri;mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ">Results: In this study, we have proposed three mathematical models for the Notch signalling pathway alone, the <span class="SpellE">Wnt</span> signalling pathway alone, and the interactions between them. These models can simulate the dynamics of the Notch and <span class="SpellE">Wnt</span> pathways in <span class="SpellE">somitogenesis</span>, and are capable of reproducing the observations derived from wet experiments. They were used to investigate the molecular mechanisms of the Notch and <span class="SpellE">Wnt</span> pathways and their crosstalk in <span class="SpellE">somitogenesis</span> through the model simulations.</span><span style="mso-ascii-font-family:Calibri; mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal"><span style="font-size:12.0pt;mso-ascii-font-family: Calibri;mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ">Conclusions: Three mathematical models are proposed for the Notch and <span class="SpellE">Wnt</span> pathways and their interaction during <span class="SpellE">somitogenesis</span>. The simulations demonstrate that the extracellular Notch and <span class="SpellE">Wnt</span> signals are essential for the oscillating expressions of both Notch and <span class="SpellE">Wnt</span> target genes. Moreover, the internal negative feedback loops and the three levels of crosstalk between these pathways play important but distinct roles in maintaining the system oscillation. In addition, the results of the parameter sensitivity analysis of the models indicate that the Notch pathway is more sensitive to perturbation in <span class="SpellE">somitogenesis</span>. (Abstract reproduced from Wang et al., 2013, with permission)</span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal"><b><span style="font-size:12.0pt;mso-ascii-font-family: Calibri;mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ"> </span></b></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;text-align: justify;line-height:normal"><span style="font-size:12.0pt;mso-ascii-font-family: Calibri;mso-fareast-font-family:"Times New Roman";mso-hansi-font-family:Calibri; mso-bidi-font-family:Calibri;color:black;mso-fareast-language:EN-NZ">* Please note that only the Notch pathway model is reproduced here.</span></p> <p class="MsoNormal" style="text-align:justify;line-height:normal"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; color:black;mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="text-align:justify;line-height:normal"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; color:black;mso-fareast-language:EN-NZ">The original paper reference is cited below:</span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ">Mathematical models for the Notch and <span class="SpellE">Wnt</span> <span class="SpellE">signaling</span> pathways and the crosstalk between them during <span class="SpellE">somitogenesis</span>, Hong-<span class="SpellE">yan</span> Wang, Yan-<span class="SpellE">xin</span> Huang, Yun-<span class="SpellE">feng</span> Qi, Yu Zhang, Yong-li <span class="SpellE">Bao</span>, Lu-<span class="SpellE">guo</span> Sun, Li-<span class="SpellE">hua</span> <span class="SpellE">Zheng</span>, Yu-<span class="SpellE">wei</span> Zhang, <span class="SpellE">Zhi-qiang</span> Ma and Yu-<span class="SpellE">xin</span> Li, 2013, <i>Theoretical Biology and Medical Modelling</i>, <span style="mso-bidi-font-weight:bold">10</span>:27  doi:10.1186/1742-4682-10-27.</span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; 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mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="font-size:12.0pt;mso-ascii-font-family:Calibri;mso-fareast-font-family: "Times New Roman";mso-hansi-font-family:Calibri;mso-bidi-font-family:Calibri; mso-fareast-language:EN-NZ"> </span></p> <p class="MsoNormal" style="margin-bottom:0cm;margin-bottom:.0001pt;line-height: 16.8pt;mso-outline-level:1;background:white;vertical-align:baseline"><span style="mso-ignore:vglayout; position:relative;z-index:251659264;left:-619px;top:72px;width:622px; height:209px"> <table cellpadding="0" cellspacing="0"> <tr> <td width="622" height="137" bgcolor="white" style="vertical-align:top;background: white"><span style="position:absolute;mso-ignore:vglayout; z-index:251659264"> <table cellpadding="0" cellspacing="0" width="100%"> <tr> <td> <div v:shape="Text_x0020_Box_x0020_2" style="padding:3.6pt 7.2pt 3.6pt 7.2pt" class="shape"> <p class="MsoNormal" style="margin-right:3.0pt;text-align:justify;tab-stops: 202.5pt 387.0pt 394.5pt"><span class="GramE">Schematic diagram of the Notch <span class="SpellE">signaling</span> pathway.</span> The diagram was created using <span class="SpellE">CellDesigner</span>. The light green rectangle represents protein; the bottle green parallelogram represents mRNA; the white rectangle that contains a light green rectangle represents a complex; <span style="font-family:"Cambria Math","serif";mso-bidi-font-family:"Cambria Math"">∅</span> represents the resultant of a degradation reaction or reactant of a combination reaction. The arrow represents the reaction. (Figure obtained from Wang H., et al., 2013, with permission)<span style="font-size:10.0pt; line-height:115%;font-family:"Garamond","serif";mso-bidi-font-family:Aharoni; color:black;mso-themecolor:text1;background:white"></span></p> <p class="MsoNormal" style="text-align:justify"> </p> </div> </td> </tr> </table> </span> </td> </tr> </table> </span> </p> </div>