Biology subjects

Lau, S.-F.

Publications and source records attributed to Lau, S.-F..

3 recordsLinked to original sources

bioRxiv2026

nELAVL phosphorylation by CDKL5 regulates inter-condensates composition and communication to promote experience-dependent maturation of the visual cortex

Mutations in Cyclin-Dependent Kinase-Like 5 (CDKL5) cause CDKL5 deficiency disorder (CDD), an X-linked neurodevelopmental condition. Through a phosphoproteomic screen, we identified the neuron-specific nELAVL family of RNA-binding proteins as direct activity-dependent substrates of CDKL5. In support of this regulatory axis, single-nuclei transcriptomics of Cdkl5 knockout (KO) cortices revealed an enriched reduction in activity-dependent mRNAs. Mechanistically, we show that nELAVL proteins undergo phase separation to form biomolecular condensates, the size of which is gated by CDKL5 phosphorylation. Loss of CDKL5 leads to enlarged nELAVL condensates, which exhibit reduced binding affinity for the target mRNA Fos, resulting in its accelerated degradation. This disruption extends to inter-condensate communication: phosphodeficient nELAVL show diminished interaction with P-bodies, which themselves become enlarged in CDD mutant iNeurons. Functionally, the absence of nELAVL phosphorylation recapitulates the deficits in experience-dependent visual function observed in Cdkl5 KO mice. Our findings establish a critical molecular mechanism by which CDKL5-mediated phosphorylation governs mRNA metabolism by tuning the properties of nELAVL condensates and their communication with other biomolecular condensates, ultimately promoting experience-dependent maturation of the visual cortex.

neuroscience↗

bioRxiv2026

Autistic Children Show Reduced Activity in Left Superior Temporal Cortex in Response to Social-emotional Meaning in Language

Autistic children often differ from non-autistic peers in social interaction, emotional processing, and language communication. While the neural differences between autistic and non-autistic children in processing paralinguistic social-emotional cues, such as emotional prosody, are well-documented, much less is known about how the brain processes the social-emotional meaning carried by the language content itself. In non-autistic adults, the left superior temporal sulcus (STS) and adjacent gyrus show a social-emotional bias, responding more strongly to social-emotional content than to content describing inanimate objects. We investigated whether this bias is present in children and whether it is altered in autistic children. We recruited 78 right-handed children who underwent functional magnetic resonance imaging (fMRI) scanning while listening to sentences describing either people in emotional situations (social-emotional sentences) or non-human objects, events, or concepts (object sentences). After excluding those with excessive head motion, we analyzed data from 58 of them (37 autistic and 21 non-autistic; mean age 10 years). Across the sample as a whole, the left STS responded more strongly to social-emotional sentences than to object sentences, indicating that this social-emotional bias is already present in childhood. Importantly, this bias was reduced in autistic children compared to non-autistic controls, whereas no group difference was observed in general auditory or lexico-syntactic processing. This reduced activity in the left STS in response to social-emotional semantics may contribute to autistic children's social communication challenges.

neuroscience↗

bioRxiv2020

High-resolution two-photon transcranial imaging of brain using direct wavefront sensing

Imaging of the brain in its native state at high resolution poses major challenges to visualization techniques. Two-photon microscopy integrated with the thinned-skull or optical clearing skull technique provides a minimally invasive tool for in vivo imaging of the cortex of mice without activating immune response and inducing brain injury. However, the imaging contrast and resolution are severely compromised by the optical heterogeneity of the skull, limiting the imaging depth to the superficial layer. Here, we develop adaptive optics two-photon microscopy for high-resolution transcranial imaging of layer 5 pyramidal neurons up to 700 m below pia in living mice. In particular, an optimized configuration of imaging system and new wavefront sensing algorithm are proposed for accurate correction for the aberrations induced by the skull window and brain tissue. We investigated microglia-plaque interaction in living brain of Alzheimers disease and demonstrated high-precision laser dendrotomy and single-spine ablation.

neuroscience↗