rstb.2019.0753.pdf (3.8 MB)
Active perception during angiogenesis: filopodia speed up Notch selection of tip cells in silico and in vivo.
journal contributionposted on 2021-02-10, 14:50 authored by Bahti Zakirov, Georgios Charalambous, Raphael Thuret, Irene M Aspalter, Kelvin Van-Vuuren, Thomas Mead, Kyle Harrington, Erzsébet Ravasz Regan, Shane Paul Herbert, Katie Bentley
How do cells make efficient collective decisions during tissue morphogenesis? Humans and other organisms use 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 through the 'basal cognitive lens' we acquire a fresh perspective on the tip cell selection process, revealing a hidden, yet vital time-keeping role for filopodia. Finally, we discuss a myriad of new and exciting research directions stemming from our conceptual approach to interpreting cell behaviour. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.
Crick (Grant ID: 10751, Grant title: Bentley FC001751)