Yep! Green are neurons, red is actin, blue DAPI

We are excited to continue working on KANSL1 for the foreseeable future and to think more broadly about the role of cilia in sociability. Thanks to our co-authors and funders including the KdVS Foundation and CZ Biohub.

This work establishes that KANSL1 functions at cilia and that this function contributes to the clinical symptomatology of KdVS. Yet again, we find that a gene associated with social behavior functions at cilia.

Perhaps this non-invasive 30 second test (used to diagnose the ciliopathy Primary Ciliary Dyskinesia) could be more broadly used for identifying additional unrecognized genetic ciliopathies.

Finally, James measured the ciliary functional biomarker nasal nitric oxide in 11 individuals with KdVS and observed they had significantly lower values compared to a direct family member.

Next we translated this work to individuals with KdVS, documenting the prevalence of cilia-associated conditions like structural heart defects, structural respiratory defects, and hypogonadism via caregiver surveys in collaboration with Anna Pfalzer and COMBINEDBrain.

Loss of Kansl1 causes ciliogenesis phenotypes that can be partially rescued by human KANSL1.

Here we show that in Xenopus, Kansl1 is highly expressed in embryonic ciliated tissues and localizes to motile ciliary axonemes and basal bodies of the epidermis. This localization was seen both with an antibody we validated and by expressing GFP-tagged human KANSL1.

Since microtubule dynamics are so essential for cilia form and function, and because folks with KdVS have many clinical symptoms associated with ciliopathies (structural heart defects etc), we hypothesized that KANSL1 functions at the cilium.

KANSL1 is best known as a chromatin regulator, but ALSO directly stabilizes microtubules at the mitotic spindle (yet another one of these “dual function” chromatin regulators).

While my lab to this point has been studying genes associated with atypical sociability (namely autism), we got interested in this gene because folks with variants in KANSL1 are atypically hypersociable. Watch them here: www.youtube.com/watch?v=6mqY...

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