Tikka Pauli, Schaefer Franz
Department of Medicine, University of Heidelberg, Heidelberg, Germany.
Methods Mol Biol. 2019;1926:235-246. doi: 10.1007/978-1-4939-9021-4_19.
This chapter reviews some currently available methodologies for constructing mathematical models in kidney development. Mammalian nephrogenesis is a complex biological process, which in its earliest stages involves migration, condensation, proliferation, and differentiation of metanephric mesenchymal (MM) cells interacting with the uroepithelial cells of the ureteric bud (UB). First, the mathematical modelling in biology is generally described. Secondly, some accounts to biological pattern formation in modelling are given in general, including models that transcend the Turing model. This is followed by a short assessment on the main branch of models in the kidney development, the evaluation of the branching morphogenesis of the kidney. Finally, two alternative models in the early kidney development processes are given as an example. They also elucidate the difficulties in the model building process. Firstly, a computational model building with the CompuCell3D program for the early nephron progenitor cell movements with the key extracellular signaling effectors is depicted. This collective migration leads to the first pretubular aggregate (PTA). The simulation parameters of the program imitate the program's cell sorting example with different adhesions and chemoattractants. The program utilizes Cellular Potts Model (CPM) to describe the development. Secondly, an example of PTA to renal vesicle (RV) transition modelling is described. In that case, the model is unique, where the model process is based on the chemoattractants from UB.
本章回顾了一些目前可用于构建肾脏发育数学模型的方法。哺乳动物肾发生是一个复杂的生物学过程,在其最早阶段涉及后肾间充质(MM)细胞与输尿管芽(UB)的尿上皮细胞相互作用的迁移、聚集、增殖和分化。首先,对生物学中的数学建模进行了总体描述。其次,对建模中的生物模式形成进行了一般性阐述,包括超越图灵模型的模型。接下来对肾脏发育模型的主要分支进行了简要评估,即对肾脏分支形态发生的评估。最后,给出了肾脏早期发育过程中的两个替代模型作为示例。它们也阐明了模型构建过程中的困难。首先,描述了使用CompuCell3D程序构建的一个计算模型,该模型用于模拟早期肾祖细胞与关键细胞外信号效应器的运动。这种集体迁移导致了第一个前肾小管聚集物(PTA)。该程序的模拟参数模仿了具有不同黏附力和化学引诱剂的程序细胞分选示例。该程序利用细胞Potts模型(CPM)来描述发育过程。其次,描述了一个从PTA到肾小囊(RV)转变建模的示例。在这种情况下,该模型是独特的,其模型过程基于来自UB的化学引诱剂。