Biology subjects

Giudicelli, F.

Publications and source records attributed to Giudicelli, F..

4 recordsLinked to original sources

bioRxiv2026

The human-specific gene FRMPD2B couples postnatal experience to the expansion of cortical connectivity

The human neocortex is characterized by its uniquely prolonged postnatal developmental period during which experience sculpts neuronal circuits, a process essential to human cognitive abilities. Yet whether human-specific genetic innovations have shaped the activity-dependent mechanisms regulating circuit assembly remains unknown. Here, we identify the human-specific gene FRMPD2B as an activity- and experience-regulated modifier of cortical connectivity. FRMPD2B is primarily expressed in cortico-cortical projection neurons postnatally and throughout childhood. It promotes dendritic, axonal and synaptic development, and is required for proper morphogenesis in xenotransplanted human cortical neurons. FRMPD2B expression is bidirectionally regulated by neuronal activity and experience. This activity-responsiveness was gained after FRMPD2B arose through partial gene duplication, when a retrotransposon insertion remodeled its promoter. Our findings highlight how a series of genetic innovations have led to the emergence of a human-specific activity-regulated developmental program through which postnatal experience drives cortical connectivity expansion, linking genome evolution to human brain plasticity.

neuroscience↗

bioRxiv2025

Salmonids reveal principles of regulatory evolution following autotetraploidization

Early vertebrate autotetraploidization events may have enabled major innovations by expanding the genetic material for functional diversification, yet their ancient timing obscures how genome doubling reshaped gene regulatory evolution. Salmonids provide a unique window to these mechanisms, because they experienced a comparatively recent autotetraploidization and are earlier in the rediploidization process - which creates new genes and regulatory elements during evolution. Here, using large-scale multiomics spanning embryonic and adult tissues in two salmonids, we investigate gene regulatory evolution following genome doubling and rediploidization, which we show is governed by developmental and tissue-specific context, with a period of maximal constraint at advanced stages of embryogenesis. This work advances understanding of vertebrate genome evolution, while providing an open resource supporting salmonid aquaculture and conservation.

evolutionary biology↗

bioRxiv2022

A key role for p60-Katanin in axon navigation is conditioned by the tubulin polyglutamylase TTLL6

The microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling of this network by selective activation of microtubule-regulating proteins, including microtubule severers, emerged as a central process in neuronal wiring. Tubulin posttranslational modifications control both microtubule properties and the activities of their interacting proteins. However, whether and how tubulin posttranslational modifications may contribute to neuronal connectivity has not yet been addressed. During zebrafish embryogenesis, we show that the microtubule severers p60-katanin and spastin play specific roles in axon guidance and identify a key role for tubulin polyglutamylation in their functional specificity. Furthermore, our work reveals that polyglutamylases with undistinguishable activities in vitro, TTLL6 and TTLL11, play exclusive roles in axon navigation by selectively tuning p60-katanin and spastin activities. We confirm the selectivity of TTLL11 towards spastin activation in mammalian cortical neurons and establish its relevance in preventing axonal degeneration triggered by spastin haploinsufficiency. Our work thus provides mechanistic insight on the control of microtubule-driven neuronal development and homeostasis, and opens novel avenues for developing therapeutic strategies in spastin-associated hereditary spastic paraplegia.

developmental biology↗

bioRxiv2018

An in vivo translation-reporter system for the study of protein synthesis in zebrafish embryos

Control of gene expression at the translation level is increasingly regarded as a key feature in many biological processes. Simple, inexpensive, and reliable procedures to visualise sites of protein production are required to allow observation of the spatiotemporal patterns of mRNA translation at subcellular resolution. We present a method, named SPoT (for Subcellular Patterns of Translation), developed upon the original TimeStamp technique (Lin et al., 2008), consisting in the expression of a fluorescent protein fused to a tagged, self-cleavable protease domain. Addition of a cell-permeable protease inhibitor instantly stabilizes newly produced, tagged protein allowing to distinguish recently synthesized protein from more ancient one. After a brief protease inhibitor treatment, the ratio of tagged vs non-tagged forms is highest at sites where proteins are the most recent, i.e. sites of synthesis. Therefore, by comparing tagged and non-tagged protein it is possible to spotlight sites of translation. By specifically expressing the SPoT cassette in neurons of transgenic zebrafish embryos, we reveal sites of neuronal protein synthesis in diverse cellular compartments during early development.

developmental biology↗