Lou Yuan, Nie Qing, Wan Frederic Y M
Department of Mathematics, The Ohio State University, Columbus, OH 43210 (
SIAM J Appl Math. 2005;65(5):1748-1771. doi: 10.1137/S0036139903433219.
Concentration gradients of morphogens are known to be instrumental in cell signaling and tissue patterning. Of interest here is how the presence of a competitor of BMP ligands affects cell signaling. The effects of Sog on the binding of Dpp with cell receptors are analyzed for dorsal-ventral morphogen gradient formation in vertebrate and Drosophila embryos. This prototype system includes diffusing ligands, degradation of morphogens, and cleavage of Dpp-Sog complexes by Tolloid to free up Dpp. Simple and biologically meaningful necessary and sufficient conditions for the existence of a steady state gradient configuration are established, and existence theorems are proved. For high Sog production rates (relative to the Dpp production rate), it is found that the steady state configuration exhibits a more intense Dpp-receptor concentration near the dorsal midline. Numerical simulations of the evolution of the system show that, beyond some threshold Sog production rate, the transient Dpp-receptor concentration at the dorsal midline would become more intense than that of the steady state, before subsiding and approaching a nonuniform steady state of lower magnitude. The magnitude of the transient concentration has been found to increase by several fold with increasing Sog production rate. The highly intense Dpp activity at and around the dorsal midline is consistent with available experimental observations and other analytical studies.
形态发生素的浓度梯度在细胞信号传导和组织模式形成中起着重要作用。这里感兴趣的是骨形态发生蛋白(BMP)配体的一种竞争者的存在如何影响细胞信号传导。分析了短 gastrulation 蛋白(Sog)对脊椎动物和果蝇胚胎背腹形态发生素梯度形成过程中Dpp与细胞受体结合的影响。这个原型系统包括扩散的配体、形态发生素的降解以及 Tolloid 对 Dpp - Sog 复合物的切割以释放出 Dpp。建立了稳态梯度构型存在的简单且具有生物学意义的充要条件,并证明了存在性定理。对于高 Sog 产生率(相对于 Dpp 产生率),发现稳态构型在背中线附近表现出更强的 Dpp - 受体浓度。该系统演化的数值模拟表明,超过某个阈值 Sog 产生率后,背中线处的瞬时 Dpp - 受体浓度在下降并接近较低幅度的非均匀稳态之前,会比稳态时更强。已发现瞬时浓度的幅度会随着 Sog 产生率的增加而增加几倍。背中线处及其周围高度强烈的 Dpp 活性与现有的实验观察和其他分析研究一致。