S Lopes Lab | Pkd2 protein affects cilia length and impacts left-righ flow dynamics

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[From left to right: Raquel Jacinto, Pedro Sampaio and Susana Lopes]

Raquel Jacinto and Pedro Sampaio, respectively former member and PhD student from the Proliferation and Fate Regulation of Stem Cells Lab led by Susana Lopes, published an article in the journal Frontiers in Cell and Developmental Biology entitled "Pkd2 Affects Cilia Length and Impacts LR Flow Dynamics and Dand5" (full article here).

In brief, Susana Lopes talks about this article:

What discoveries led you to the research described in your publication?
We were not expecting cilia length to be affected by lack of a protein called Pkd2 as it was not reported before, and decided to explore this result.

What were you trying to understand and what is the main discovery of this work?
We were trying to compare mechanosensing with chemosensing during the left-right development using zebrafish mutants for ciliary motility and for ciliary mechanosensing.

Why is this important?
Our results are important because there is a debate on the etiology of vertebrate laterality and it is still a mystery if the initial process mediated by motile cilia results in a mechanical or chemical stimulus. So we were trying to inhibit each of these mechanisms on its own and compare the outcomes, namely the number of times the organs would be wrongly placed (i.e. hearts on the right side).

Can you use an analogy to help us understand your work?
Our body starts by being symmetric, meaning no right nor left sides exist. The left and the right side of our body are defined during embryonic development. However, the initial steps of this process are not well understood. They involve an embryonic organ that later disappears. The organ is called left-right-organizer (LRO) and has many motile cilia that will organize our body axis, like a GPS provides coordinates to a driver. Motile cilia generate flows of body fluids and we are trying to understand if those flows trigger mechanical cues or transport signaling molecules as cues. The results of the flow action are going to be the coordinates for the first asymmetric gene to be expressed only on the left side of the embryo. This will eventually lead to the correct localization of the heart on the left side.

What questions remain to be asked?
We still need to unerstand how is Pkd2 regulating cilia length and what is intracellular calcium triggering.

Find out more about Cilia Regulation and Disease Lab.

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