This represents a further step forward in understanding the time-course and spatial pattern of brain development on the systems level. As the authors of the study noted, the mathematical model could also be used to gain information about other biological pattern-forming processes. (PLoS Computational Biology)
Scientists of the Institute of Bioinformatics and Systems Biology (IBIS) and the Institute of Developmental Genetics (IDG) at Helmholtz Zentrum München have together created a mathematical model of the gene activities in the region of the mid- hindbrain boundary (MHB). It shows the time-course and spatial pattern of development from the eighth to the tenth day of embryonic development in the mouse. “Our model is one of the first to correctly predict the natural courses of brain development in a qualitative simulation,” Fabian Theis said.
Embryonic brain development in vertebrates begins very early in different precursor stages. Here the prospective mid-hindbrain boundary is of key importance. Experimental data shows that the midbrain and hindbrain regions differ with respect to the most important eight genes which are active there. On the basis of these data a mathematical model was devised, and a qualitative computational model of the regulatory network was developed. First, the researchers started from the simplified assumption that the respective genes are either active or not. Already in this qualitative model, key regulatory interactions became evident which are necessary for the maintenance of the midbrain-hindbrain boundary. One of the findings which was later confirmed experimentally involved two signal proteins: Fgf8 is necessary for maintaining Wnt1 expression, but does not induce it. The further developed model includes the amount of gene expression and correctly simulates the processes of embryonic development between day 8 and day 10 both temporally and spatially.
After further successful simulations the Helmholtz researchers are not only convinced that their method can be extended to other biological pattern-forming processes, but also that qualitative experimental data provide a suitable basis for mathematical models.
Original Publication: Wittmann DM, Blöchl F, Trümbach D, Wurst W, Prakash N, Theis FJ. (2009) Spatial Analysis of Expression Patterns Predicts Genetic Interactions at the Mid-Hindbrain Boundary. PLoS Comput Biol 5(11): e1000569. doi:10.1371/journal.pcbi.1000569, http://www.ploscompbiol.org/doi/pcbi.1000569
Helmholtz Zentrum München is the German Research Center for Environmental Health. As leading center oriented toward Environmental Health, it focuses on chronic and complex diseases which develop from the interaction of environmental factors and individual genetic disposition. Helmholtz Zentrum München has around 1700 staff members. The head office of the center is located in Neuherberg to the north of Munich on a 50-hectare research campus. Helmholtz Zentrum München belongs to the Helmholtz Association, Germany’s largest research organization, a community of 16 scientific-technical and medical-biological research centers with a total of 26,500 staff members.
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