Active Perception during Angiogenesis: Filopodia speed up Notch selection of tip cells in silico and in vivo

How do cells make efficient collective decisions during tissue morphogenesis? Humans and other organisms utilize feedback between movement and sensing known as sensorimotor coordination or active perception to inform behaviour, but active perception has not before been investigated at a cellular level within organs. Here we provide the first proof of concept in silico/in vivo study demonstrating that filopodia (actin-rich, dynamic, finger like cell-membrane protrusions) play an unexpected role in speeding up collective endothelial decisions during the time-constrained process of tip cell selection during blood vessel formation (angiogenesis). We first validate simulation predictions in vivo with live imaging of zebrafish intersegmental vessel growth. Further simulation studies then indicate the effect is due to the coupled positive feedback between movement and sensing on filopodia conferring a bistable switch-like property to Notch lateral inhibition, ensuring tip selection is a rapid and robust process. We then employ measures from computational neuroscience to assess whether filopodia function as a primitive ( basal) form of active perception and find evidence in support. By viewing cell behaviour in tissues through the basal cognitive lens we acquire a fresh perspective on not only the well-studied tip cell selection process, revealing a hidden, yet vital, time-keeping role for filopodia, but on how to interpret and understand cell behaviour in general, opening up a myriad of new and exciting research directions.