Subcellular compartmentalization expands the regulatory repertoire of a conserved developmental network

Abstract

How can a conserved network orchestrate precise local outcomes across a wide array of developmental and ecological contexts during evolution? Flexible subcellular compartmentalization of multivalent proteins is a powerful, but understudied, driver of dynamic modularity in regulatory networks, defining an architecture in which context-sensing bridges between distributed subnetworks allow simultaneous access to alternative regulatory states. Here we construct one of the most complete atlases of avian beak morphogenesis and examine how subcellular compartmentalization modulates regulatory repertoire of the conserved protein network across hundreds of developmental contexts. We find that, in both jaws, the network is comprised of a hub of autoregulatory, context-sensing proteins whose links to a context-invariant core depends on subcellular colocalization. We show that proteins in this hub more than double the networks regulatory repertoire by unlocking latent coexpression states allowing concurrent tissue divergence. We demonstrate that in this architecture, specialization does not interfere with changeability, enabling a compact network to achieve remarkable tissue diversification and developmental expansion. The regulatory autonomy of the hub proteins and their ability to convert a wide range of inputs underpin robustness of developmental systems. Ultimately, such organization can reconcile ecological precision with the evolutionary lability evident in avian beak diversification.