iiinova — where your digital self keeps evolving

Reposted by Sara Zeppilli

Debby Silver @debbysilver.bsky.social · 10/08/2025

Sharing our newest study led by the incredibly talented @federicamosti.bsky.social investigating new molecular mechanisms of human brain development. We discover a human-specific enhancer HAR1984 that influences chromatin looping to promote cortical size and folding! www.biorxiv.org/cgi/content/...

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Sara Zeppilli @sarazeppilli.bsky.social · 12/07/2025

It was an honor to be part of such an amazing Cajal course on synapse biology, amazing lineup of speakers and projects, and to connect with Europe! A big thank to the organizers Cecile Charrier and Julien Dupuis and to all the instructors!

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Sara Zeppilli @sarazeppilli.bsky.social · 09/04/2025

Thank you @carneyinstitute.bsky.social for summarizing our paper on the olfactory cortex for a broader audience!

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

14🧵Perhaps “teaching old cells and old genes new tricks"?

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

13🧵Olfaction is processed more broadly in cortices of amphibians but shifted to lateral areas in reptiles and mammals. Ancestral gene regulatory networks, whose signatures are still present in the olfactory cortex, may have been repurposed to diversify the early cerebral cortex

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

12🧵These results suggest there is something deeply conserved in the molecular code between olfactory cortex neurons and non-mammalian cortical neurons, extending beyond function, while neurons of the mammalian neocortex drastically diverged over the past 200 million years!

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

11🧵Last but not least, olfactory cortex neurons exhibited greater similarity to neurons of reptiles and amphibians than to neighboring neocortex neurons. Surprisingly, this similarity extended to non-mammalian neurons located outside olfactory regions!

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

10🧵We also found a small but significant difference in the neuronal composition of the olfactory cortex—but not of the neocortex—between lab and wild mice, and between human individuals, potentially driven by the differentiation of a small population of adult immature neurons!

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

9🧵Olfactory cortex glutamatergic neurons exhibit greater overlap in gene expression and lower transcriptional repression, which may suggest less functional cellular specialization and diversification in the adult olfactory cortex.

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

8🧵Ancestral cellular and molecular features in the olfactory cortex, compared to the neocortex, include graded transcriptomic profiles, greater overlap in gene expression, divergence between laboratory and wild mice, and greater similarity to cortical neurons of non-mammals.

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

7🧵We then compared neurons of the olfactory cortex with neurons of the neocortex in mice and with neurons of the cerebral cortex of reptiles and salamanders. These comparisons reveal that olfactory cortex neurons retained ancestral features of cortical identity🦖

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

6🧵First, for the olfactory cortex aficionados, we here provide a detailed molecular characterization of cell types, their markers, and their laminar locations across the anterior-posterior axis of the brain.

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

5🧵In this study, we used single-nucleus multiome sequencing (transcriptome and epigenome) across mammalian cortical structures with different layers, with a focus on the anterior and posterior olfactory cortex.

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

4🧵The mammalian olfactory cortex provides a unique lens to understand the evolution of the cerebral cortex, with its cytoarchitecture conserved across species, while its neurons evolved alongside the emergence of the neocortex! 🔍

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

3🧵However, despite 200 million years of side-by-side coevolution with the neocortex, the mammalian olfactory cortex retained a three-layered structure, similar to the entire cerebral cortex of reptiles and amphibians. Why does this matter?

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

2🧵Olfactory regions dominated the cerebral cortex in early vertebrates. Over time, the cortex diversified extensively for processing various sensory stimuli. The most dramatic structural change in the brain? The evolution of the neocortex in mammals with its six layers! 🧠✨

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

1🧵Sensory systems evolved to help animals adapt to their environments. For example, when life transitioned from water to land, olfactory circuits adapted to help find food, detect predators, and locate mates. 🦸‍♂️

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Sara Zeppilli @sarazeppilli.bsky.social · 08/04/2025

Happy to see my PhD work in the Fleischmann lab at Brown University @carneyinstitute.bsky.social published in @natureneuro.bsky.social! -Single-cell genomics of the mouse olfactory cortex reveals contrasts with neocortex and ancestral signatures of cell type evolution nature.com/articles/s41...

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Reposted by Sara Zeppilli

Stein Aerts @steinaerts.bsky.social · 14/02/2025

.. and what an honour to be jointly published with two other papers from the @kaessmannlab.bsky.social and the Fernando García-Moreno lab - all of this summarized in a great perspective by Maria Tosches and @giacomogattoni.bsky.social www.science.org/doi/10.1126/...

science.org

Constrained roads to complex brains

Neural development and brain circuit evolution converged in birds and mammals

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