Landman Kerry A, Simpson Matthew J, Newgreen Donald F
Department of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria 3052, Australia.
Dev Growth Differ. 2007 May;49(4):277-86. doi: 10.1111/j.1440-169X.2007.00929.x.
The vertebrate enteric nervous system is formed by a rostro-caudally directed invasion of the embryonic gastrointestinal mesenchyme by neural crest cells. Failure to complete this invasion results in the distal intestine lacking intrinsic neurons. This potentially fatal condition is called Hirschsprung's Disease. A mathematical model of cell invasion incorporating cell motility and proliferation of neural crest cells to a carrying capacity predicted invasion outcomes to imagined manipulations, and these manipulations were tested experimentally. Mathematical and experimental results agreed. The results show that the directional invasion is chiefly driven by neural crest cell proliferation. Moreover, this proliferation occurs in a small region at the wavefront of the invading population. These results provide an understanding of why many genes implicated in Hirschsprung's Disease influence neural crest population size. In addition, during in vivo development the underlying gut tissues are growing simultaneously as the neural crest cell invasion proceeds. The interactions between proliferation, motility and gut growth dictate whether or not complete colonization is successful. Mathematical modeling provides insights into the conditions required for complete colonization or a Hirschsprung's-like deficiency. Experimental evidence supports the hypotheses suggested by the modeling.
脊椎动物的肠神经系统由神经嵴细胞沿头-尾方向侵入胚胎期胃肠道间充质而形成。未能完成这种侵入会导致远端肠道缺乏内在神经元。这种潜在致命的病症被称为先天性巨结肠症。一个包含神经嵴细胞的细胞运动性和增殖至承载能力的细胞侵入数学模型预测了对假想操作的侵入结果，并且对这些操作进行了实验测试。数学和实验结果一致。结果表明，定向侵入主要由神经嵴细胞增殖驱动。此外，这种增殖发生在侵入群体前沿的一个小区域。这些结果有助于理解为什么许多与先天性巨结肠症相关的基因会影响神经嵴群体的大小。另外，在体内发育过程中，随着神经嵴细胞侵入的进行，潜在的肠道组织也在同时生长。增殖、运动性和肠道生长之间的相互作用决定了完全定植是否成功。数学建模为完全定植或类似先天性巨结肠症的缺陷所需的条件提供了见解。实验证据支持了建模所提出的假设。
