Birthdate-specific plasticity of cortical neurons

Diplôme Thèse Birthdate-specific plasticity of cortical neurons eng 2026-03-13 2026-03-13 author Balavoine Eline 955652 director Jabaudon Denis 0000-0003-2438-4769 682473 Département de neurosciences fondamentales (NEUFO) 10.13097/archive-ouverte/unige:193536 urn:nbn:ch:unige-1935365 Neur. 475 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. Neurogenesis Transplantations Dewey 616.8 53 Département de neurosciences fondamentales 21A false 540 Neurobiologie développementale et plasticité 880 e3904399-8560-489f-99fe-87706eca04ab Thesis Public Thesis_manuscript_Eline_Balavoine_f.pdf 18874821 application/pdf a954bf4d987e20d32c8e42195b50e60d3b1b9fd566d5ca5ff44e535e6759713a 35b7dad0-01df-4ed0-8bae-1a46eca7fc00 Imprimatur Public BALAVOINE_Eline_475_-_Imprimatur_fi.pdf 87588 application/pdf 9781aae056f4f4cd51ba903d62a949661e70f32e224a12451ebab5d8f0a8fa5f openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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