Molecular Memory of Morphologies by Septins during Neuron Generation Allows Early Polarity Inheritance

Orateur : Julien FALK (Institut NeuroMyoGene, Lyon)

Neurite formation is a crucial stage of neuronal differentiation. However, the mechanisms that determine how and at which position neurites emerge are still poorly understood. We investigated neurite initiation in chick dorsal root ganglion (DRG) neurons. Time course analysis of cell morphologies in nascent ganglia suggests that initiation sites are induced at specific positions. The neural crest cells (NCC) migrate into the DRG ganglion and either differentiate directly into neurons or divide within the ganglia. Using live imaging of chick embryo slices, we found that bipolar neurons born in the ganglia arise from bipolar NCC progenitors. Although, these progenitors retract their processes during mitosis, the daughter cells emit processes from the same locations as the progenitor. Thus, the DRG offer an interesting model to study inheritance of morphological polarity over cell generations and across morphological transitions. We postulated that a molecular polarity could store the initial morphological polarity of NCC progenitors to mark the initiation sites of future neurites. Interestingly, molecular polarity has been evidenced during yeast budding, which occurs at specific positions relatively to the previous bud site. Septins GTP-ases that contribute to control bud site location in yeast, are involved in many polarity-related functions in mammalian cells and are expressed in chick DRG at early stages. Monitoring of septin 7 in bipolar NCC progenitors undergoing mitosis, indicates that Septin 7 accumulate at the base of retracting processes during rounding, tagging the sites from which processes will be re-initiated after division. Inhibiting Septin functions impairs neurite formation and inheritance of initiation site. Thus, Septins could contribute to store polarity features during mitotic rounding to enable daughter cells to reconstitute the initial progenitor morphology and initiate neurites.

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