Filopodia, active perception and tip cell selection (Notch)

Zakirov and colleagues (2021) began with a question about tissue morphogenesis: how do cells make efficient collective decisions? They note that humans and other organisms use sensorimotor coordination, also called active perception, to inform behaviour. They state that it had not before been investigated at a cellular level within organs.² Their case is tip cell selection, a time-constrained step in blood vessel formation, or angiogenesis. They describe their work as a proof of concept combining simulation with live imaging of intersegmental vessel growth in zebrafish. They report that simulation predictions were validated in vivo.²

Further simulation studies led Zakirov and colleagues to a mechanism. They attribute the effect to coupled positive feedback between movement and sensing on filopodia. Further simulation studies indicate that this feedback confers a bistable, switch-like property on Notch lateral inhibition. In their account, it ensures that tip selection is rapid and robust.³ The authors frame the finding as filopodia speeding up a decision.²

Work on bioelectricity also discusses Notch. George and Bates (2022) describe Notch as a conserved pathway. Its ligands are transmembrane proteins, so it acts as a short-range signal.⁵ In HEK293 cells and myocytes, raised Notch signalling was associated with more cytosolic calcium and less potassium flux. They suggest that Notch signalling may both regulate and be regulated by ion channel function.⁶ Monteiro and colleagues (2014) cite earlier work showing that the V-ATPase proton pump is essential for activation of Wnt, JNK and Notch signalling, by regulating endosomal pH.¹

Zakirov and colleagues state the larger question directly. They ask whether filopodia are a form of active perception, akin to a basal cognitive function that lets endothelial cells adapt to changing local conditions by deciding faster and more efficiently.⁴ O'Hara-Wright and colleagues (2022) note that bioelectric signals are reported to influence angiogenesis, citing other work such as Wei et al. 2020.⁷ Iorio and colleagues (2024) note that Myo10 is needed for both filopodia and tunneling nanotube formation.⁸