Doctoral thesis
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Birthdate-specific plasticity of cortical neurons

ContributorsBalavoine, Eline
Imprimatur date2026-03-13
Defense date2026-03-13
Abstract

Cortical neurons exhibit extensive diversity in their molecular identity, morphology, electrophysiological profile, and connectivity. This diversity starts to be shaped pre-mitotically at the progenitor stage by a series of temporal processes, but also relies on cell-extrinsic processes post-mitotically to refine final neuronal identity. The extent to which the micro- environment of a post-mitotic neuron contributes to shaping its identity remains unclear. To address this question, we developed a heterochronic transplantation paradigm to investigate how birthdate and laminar position shape neuronal identity during postnatal development. We challenged the laminar position of early-born neurons (E13.5) and late-born neurons (E15.5) - isolated by isochronic labelling with FlashTag - by transplanting them in a novel cortical environment. We assessed their identity before and after transplantation, in relation to their birthdate and laminar position, by examining their molecular, transcriptomic, electrophysiological, and morphological profile. By first performing scRNAseq of the donor cells, we found that newly born neurons are mostly undifferentiated at the time of transplantation. We then performed patch-sequencing of transplanted neurons integrated in Layer 2/3 and 5, and found a birth-date-specific plasticity of transplanted neurons with minimal impact of the laminar environment on projection neuron types. E13-born neurons acquire diverse transcriptomic identities, while late-born neurons seem restricted to a superficial layer fate. Together, our findings provide new insight into the developmental timing of fate commitment and the limits of post-mitotic environment-dependent plasticity in cortical neurons.

Keywords
  • Neurogenesis
  • Transplantations
Citation (ISO format)
BALAVOINE, Eline. Birthdate-specific plasticity of cortical neurons. Thèse, 2026. doi: 10.13097/archive-ouverte/unige:193536
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