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

Bahti Zakirov, Georgios Charalambous, Raphael Thuret, Irene Aspalter, Kelvin Van-Vuuren, Thomas Mead, Kyle Harrington, Erzsébet Ravasz Regan, Shane Herbert, Katie Bentley

Research output: Contribution to journalArticlepeer-review


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 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.
Original languageEnglish
JournalPhilosophical Transactions of the Royal Society B
Issue number1821
Publication statusPublished - 8 Feb 2021


Dive into the research topics of 'Active Perception during Angiogenesis: Filopodia speed up Notch selection of tip cells in silico and in vivo'. Together they form a unique fingerprint.

Cite this