Eigengene reveals invariant global spatial patterns across mouse and fish brain development

Development from a zygote to an adult organism involves complex interactions among thousands of genes. These genes exhibit highly dynamic expression across space and time. Here we report a striking simplicity amidst this complexity: Despite individual gene expression variability, the eigengene —the principal component of gene expression—exhibits an invariant global spatial pattern throughout the embryonic and post-natal stages of the mouse brain. Furthermore, the mouse pattern is observed also in the larval zebrafish, revealing that eigengene expression is conserved over 400 million years of evolution. We show that the eigengene pattern can be explained by a simple lineage model in which daughter cells’ gene expression is similar to that of their parent, but cannot be explained by one in which gene expression arises through local cellular signaling. The constrained lineage gives rise naturally to a global eigengene expression hierarchy that could aid in the formation of a spatial hierarchy of long-range signal gradients. We propose that lineage thus induces an address-like organization, which could have been co-opted by evolution for developmental processes that require positional information over a wide range of spatial scales, such as tissue patterning and axon navigation.