Tau tubulin kinase 1 and 2 regulate ciliogenesis and human pluripotent stem cells-derived neural rosettes

Bino, L.; Cajanek, L.

doi:10.1101/2023.01.18.524283

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bioRxiv · 10.1101/2023.01.18.524283

Tau tubulin kinase 1 and 2 regulate ciliogenesis and human pluripotent stem cells-derived neural rosettes

Bino, L.·Cajanek, L.

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Abstract

Primary cilia are key regulators of embryo development and tissue homeostasis. However, their mechanisms and functions, particularly in the context of human cells, are still unclear. Here, we analyzed the consequences of primary cilia modulation for human pluripotent stem cells (hPSCs) proliferation and differentiation. We show that neither activation of the cilia-associated Hedgehog signaling pathway nor ablation of primary cilia by CRISPR gene editing to knockout Tau Tubulin Kinase 2 (TTBK2), a crucial ciliogenesis regulator, affects the selfrenewal of hPSCs. In addition, we demonstrate that TTBK1, a closely related kinase without previous links to ciliogenesis, is upregulated during hPSCs-derived neural rosette differentiation to regulate primary cilia formation together with TTBK2. Finally, we show that TTBK1/2 and primary cilia are implicated in the regulation of the size of hPSCs-derived neural rosettes.

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Bino, L., Cajanek, L.. 2023-01-19. Tau tubulin kinase 1 and 2 regulate ciliogenesis and human pluripotent stem cells-derived neural rosettes. https://doi.org/10.1101/2023.01.18.524283

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