Lehtinen Lab
@LehtinenLab
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basic & translational research on CSF-based signaling & choroid plexus • find us @HMS_Neuro & @BostonChildrens Pathology Dept • // account run by lab members
Boston, MA
Joined December 2019
RT @ScienceYael: My first journal cover :) . Volume 28 Issue 7, July 2025. @NatureNeuro @LehtinenLab .
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Funded by @NIH, @NSF, @HHMINEWS, @BostonChildrens, @iddrc_bch, @SimonsFdn Autism Research Initiative, @harvardbrainsci, @NYSCSF, and more! Grateful to the public and private institutions that made this possible.
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HUGE thank you to our collaborators on this project, without whom none of this beautiful work would be possible: Joshua Head, @Freshdipley, @NeilCDani1, Olga Chechneva, @MJHoltzmanlab, @csadegh, and Towia Libermann. @BCH_InTheNews.
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We uncovered a new serotonergic axis — from the ChP to the CSF — that sculpts the developing brain. It’s powerful, fast, and vulnerable to disruption. This work opens a new window into how 🤰 influence lifelong brain function. 📖 Full paper:
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Maternal exposure to the psychedelic LSD triggered the same ChP secretory response. Within 30 minutes, nearly 70% of embryonic ChP cells formed aposomes. This suggests serotonergic drugs in pregnancy may directly alter brain development via the CSF.
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These brain changes translated into long-term behavioral effects. Mice exposed in utero to repeated ChP activation showed:.⬇ Less social interaction.⬇Fewer repetitive behaviors.– Altered courtship vocalizations.Neurodevelopmental outcomes, shifted before birth.
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Apocrine secretion didn’t just reshape the cortex, it altered proliferation in the lateral ganglionic eminence (LGE) too. We saw shifts in interneurons, glia, and microglia. This pathway impacts multiple brain regions and cell types during development.
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When we triggered ChP secretion during neurogenesis, the consequences were striking. We saw shifts in neuronal fate:.⬆ SATB2+ callosal projection neurons.⬇ TBR1+ corticothalamic neurons.These changes were layer-specific — reorganizing cortical architecture at its foundation.
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Apocrine secretion changes the composition of the CSF in minutes. We found a surge of key developmental signals including IGF2, Sonic Hedgehog (SHH), insulin, & transthyretin (TTR). Each of these proteins is known to shape how neural progenitors divide and differentiate.
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So what sets off this secretory burst? Among other things, activation of the serotonin receptor 5-HT2C. We showed that stimulating 5-HT2C triggers a wave of calcium signaling followed by apocrine secretion in the embryonic ChP, flooding the CSF w key developmental signals.
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Balloon-like structures, called aposomes, form at the surface of ChP cells & release huge amounts of protein directly into the CSF. This is a high-volume, coordinated secretion mechanism, & it massively expands our understanding of how the ChP contributes to brain development.
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We discovered the choroid plexus (ChP) doesn’t just secrete tiny vesicles & exosomes. It also unleashes large apocrine secretory structures packed with proteins that flood cerebrospinal fluid (CSF) during brain development. This changes how we think about embryonic 🧠 signaling.
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Led by @ScienceYael and out today in @NatureNeuro: the brain's fluid-secreting organ — the choroid plexus — can reshape neural development through a powerful, little-known process. & it can be hijacked by serotonergic drugs like LSD. 🧠👇 A thread
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Check out our new 🌟 STAR protocol 🌟 on dissecting, immunostaining, and imaging whole-mount LV, 3V, & 4V ChP in adult & embryonic mice by @LillianByer & @Huixin_BJ!.
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🌟Check out @HydroAssoc white paper on research priorities for hydrocephalus from current (@Alex_H_Bio and @chehnly1) and previous (@csadegh) lab members as well as our awesome hydrocephalus colleagues! 🧠💦
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🌟Review alert: @Huixin_BJ & @chehnly1 contextualize recent findings of ChP core functions, response to neuroinflammatory conditions, outstanding questions, and future tools needed!
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RT @ScienceYael: So so so honored to be featured in @SfNtweets Newsletter as part of the Future of Neuroscience! If you want to know a lit….
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🌟 Review alert: Curious about the role of the ChP in multiple sclerosis (MS) neuropathology🧠? .Check out @Alex_H_Bio review on how the ChP regulates CSF💧immune infiltration and signature + contributes to CSF composition in MS.
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🌟Check out this thread from recent PhD graduate @ScienceYael, who led this wonderful review about the roles of the choroid plexus in disease! 🧠.
🧵1/ 🚨 TL cleanse good news! 🚨 Excited to share our review, Choroid Plexus Pathophysiology, now out in Annual Review of Pathology! 🧠 The ChP plays critical roles in CNS health, disease, and maybe therapy.
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