Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation

Abstract

Pyramidal neurons are the major cell type of the forebrain, consisting of a pyramidally shaped soma with axonal and apicobasal dendritic processes. It is poorly understood how the neuronal soma morphs from a sphere to pyramid, while generating neurites of the proper shape and orientation. Here, we discovered that the spherical somata of immature neurite-less neurons possess a circumferential wreath-like network of septin filaments, which promotes myosin II localization and suppresses Arp2/3 activity at the base of filopodial actin bundles. The septin network facilitates neurite formation by stabilizing nascent filopodia, which mature to neurites, and concomitantly maintains a consolidated soma by suppressing the extension of lamellipodia. We show that this septin function is critical for the morphogenesis and spatial orientation of pyramidal somata and their neurites in vitro and in vivo. Therefore, the somatic septin cytoskeleton provides a key morphogenetic mechanism for neuritogenesis and the development of pyramidal neurons. Highlights- A septin wreath-like network controls the shape of neuronal somata and nascent neurites - Septins promote and suppress filopodial and lamellipodial protrusions, respectively - Septins scaffold myosin II and exclude Arp2/3 at the base of filopodial actin - Development of pyramidally shaped neurons requires septins in vitro and in vivo eTOC SummaryRadler et al report a new morphogenetic mechanism in the development of pyramidal neurons, which is mediated by a septin wreath-like cytoskeleton in the soma of immature spherical neurons. The septin network stabilizes somatic filopodia and suppresses lamellipodia by differentially controlling the localization of myosin II and Arp2/3.