Proud to share our latest bioRxiv with Lakatos lab @LakatosLab...
Srinjan Lab @srinjan.bsky.social@srinjan_basu
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Jul 30, 2026
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Proud to share our latest bioRxiv with Lakatos lab @LakatosLab showing how niche-specific mechanotransduction guides human cortical patterning and cell fate acquisition. How does a tissue's mechanical environment shape which cells it makes, and when? 1/n
biorxiv.org/content/10.648…
biorxiv.org/content/10.648…
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🧠🧫 We use cortical brain organoids and a dominant-negative LINC complex to decouple single cells from cytoskeletal force transmission as they move from the dense ventricular zone (VZ) to the sparse cortical plate (CP) - creating mechanically "blind" cells in normal tissue. 2/n
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LINC-decoupled cells lose nuclear shape and local alignment specifically at the VZ-CP boundary, prematurely delaminate from the VZ, and end up mispositioned later in development. 3/n
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⚖️ Decoupled cells fail to acquire intermediate progenitor identity, instead adopting a biased neuronal fate skewed toward deep-layer at the expense of upper-layer identity - a phenotype that persists rather than resolves with extended culture. 4/n
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🧬 Integrating transcriptomic data with a spatial atlas of developing human fetal cortex reveals impaired density-sensing and ERK activity in LINC-decoupled cells, directly implicating altered mechanosensation in fate allocation. 5/n
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This links to emerin mislocalisation at the nuclear envelope and altered histone mark deposition - showing how mechanical heterogeneity in a developing tissue may directly instruct cell fate 6/n
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🧑🤝🧑Some great work led by our PhD student Alex @alexjkingston with help from Annabelle @AnnabelWurmser, Gökçe @gokceagsu and others in the labs.
Thanks to great support @ImperialLifeSci @SCICambridge Cambridge Clinical Neuroscience and from funders @wellcometrust @UKRI_News 7/n
Thanks to great support @ImperialLifeSci @SCICambridge Cambridge Clinical Neuroscience and from funders @wellcometrust @UKRI_News 7/n