Section: New Results

Network inference for mammalian cortex development

participants: A Crombach

The mammalian cortex divides into two major regions, neocortex (NCx) and the structurally simpler allocortex. Whereas NCx is well-characterized, the allocortex is much less studied. Its best known region is the olfactory (piriform, PCx) cortex. The regions have a laminar structure, with distinct neuronal cell types in each of the layers: NCx has 6 layers, PCx has 3. The differentiation of precursor cells into various neuronal cell types determines to which layer these cells will migrate. This process is mostly studied in NCx and depends on the activity of  10–20 developmental genes. In PCx the same genes are used, yet they appear in other combinations and may indicate diverse target layers, sometimes violating rules-of-thumb derived from NCx. Current understanding is rather incomplete with respect to how cortical neurons are specified. We propose that, despite apparent contradictions, a single gene network can explain the development of distinct cortical regions.

In collaboration with Dr. A. Fleischmann at Brown University (USA), we are measuring the expression of genes involved in neurodevelopment at cellular resolution using light-sheet microscopy. These data will form the basis for the inference of a regulatory network describing neuronal differentiation in NCx and PCx. Inference is done by fitting mathematical models of gene regulation to the data using global optimization methods. Currently, we are processing the image data. Moreover, single cell RNA sequencing will allow the study of the temporal dynamics of the expression of these genes and many others. We are completing an in-depth statistical analysis of the resulting genome-wide expression data.