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bioRxiv · 10.1101/2023.01.12.523739

Leftward transfer of a chemosensory polycystin initiates left-dominant calcium signaling for lateralized embryonic development

Tanaka, Y.·Morozumi, A.·Hirokawa, N.
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Abstract

Left-dominant [Ca2+]i elevation on the margin of ventral node furnishes the initial laterality signaling in mouse embryos. It depends on nodal flow, FGFR signaling, and PKD1L1-containing polycystin channels, of which interrelationship is still missing. Here we show that PKD1L1 protein is predominantly accumulated on the left margin of the nodal pit and serves as a chemosensory channel for Nodal-mediated [Ca2+]i elevation. PKD1L1/PKD2 overexpression augmented the Nodal sensitivity of fibroblasts. We detected PKD1L1-containing fragile meshwork of fibrous strands using KikGR-PKD1L1 knockin mice, especially when the extraembryonic membrane was preserved. The portion of meshwork bridging over nodal crown cells significantly lateralized to the left. This bridge was formed by a leftward flow of PKD1L1-containing fibrous strands, which can be suppressed by the FGFR inhibitor SU5402 that antagonized the [Ca2+]i elevation as well. These data provide evidence for a leftward transfer of chemosensory PKD1L1 polycystin channel, as a readout mechanism of nodal flow.

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Tanaka, Y., Morozumi, A., Hirokawa, N.. 2023-01-12. Leftward transfer of a chemosensory polycystin initiates left-dominant calcium signaling for lateralized embryonic development. https://doi.org/10.1101/2023.01.12.523739

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