A lineage-based model of scalable positional information in vertebrate brain development

The development of an adult brain from a single zygote requires cells and axons to organize in precise spatial patterns over long distances. Most mechanisms for positional information rely on diffusible molecular cues that move through the tissue, fundamentally limiting the pattern's ability to scale over the requisite orders of magnitude. Here, we propose a complementary mechanism in which positional information is inherited through the cell lineage, rather than transmitted through extracellular signals, thereby avoiding these scaling constraints. Analyzing brain-wide developmental expression in mouse and larval zebrafish, we find that principal eigengenes-co-expression patterns across thousands of genes-span multiple spatial scales, remain stable over development, and are conserved across species. Moreover, small subsets of genes can decode eigengenes, yielding multi-scale positional information. Together, these findings suggest a lineage-based mechanism for scalable positional information that complements diffusion-based mechanisms and offers a general framework for tissue patterning.