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Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation
Journal article   Open access   Peer reviewed

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

Megan R. Radler, Xiaonan Liu, Megan Peng, Brenna Doyle, Kazuhito Toyo-Oka and Elias T. Spiliotis
Current biology, v 33(3), pp 434-448
06 Feb 2023
DOI: https://doi.org/10.1016/j.cub.2022.11.043
PMID: 36538929
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1101/2022.06.19.496721View
SubmittedOpen Access (License Unspecified),  Open

Abstract

actin Arp2/3 axons dendrites filopodia lamellipodia myosin II neuritogenesis pyramidal neuron morphogenesis septins
Pyramidal neurons are a 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 develops its pyramidal morphology, 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 neuritogenesis by balancing the protrusive activity of lamellipodia and filopodia. In embryonic rat hippocampal and mouse cortical neurons, the septin wreath network consists of curvilinear filaments that contain septins 5, 7, and 11 (Sept5/7/11). The Sept5/7/11 wreath network demarcates a zone of myosin II enrichment and Arp2/3 diminution at the base of filopodial actin bundles. In Sept7-depleted neurons, cell bodies are enlarged with hyperextended lamellae and abnormally shaped neurites that originate from lamellipodia. This phenotype is accompanied by diminished myosin II and filopodia lifetimes and increased Arp2/3 and lamellipodial activity. Inhibition of Arp2/3 rescues soma and neurite phenotypes, indicating that the septin wreath network suppresses the extension of lamellipodia, facilitating the formation of neurites from the filopodia of a consolidated soma. We show that this septin function is critical for developing a pyramidally shaped soma with properly distributed and oriented dendrites in cultured rat hippocampal neurons and in vivo in mouse perinatal cortical neurons. Therefore, the somatic septin cytoskeleton provides a key morphogenetic mechanism for neuritogenesis and the development of pyramidal neurons. [Display omitted] •A septin wreath-like network controls the shape of neuronal somata and 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 Radler et al. report a septin wreath-like cytoskeleton in the soma of immature neurons that promotes neurite formation by balancing the protrusive activity of lamellipodia and filopodia. The septin network is critical for developing a pyramidally shaped soma with properly distributed and oriented dendrites.

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Web of Science research areas
Biochemistry & Molecular Biology
Biology
Cell Biology
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