This project was definitely a joint effort by multiple people. A huge thank you to all the members of Brian Mitchell’s lab at Northwestern University, and a very special thank you to the other co-first authors, Jennifer Sheridan and Julia Dorr!

Our work suggests that although AK7 localizes at cilia, it has a non-ciliary function too, related to centriole maturation. We propose that the centriolar defects underlie much of the reduction in cilia number, contributing to the loss of mucociliary flow in AK7-depleted tissues, indicative of PCD.

We observed that AK7 depletion leads to defects in centriole docking, with centrioles remaining sub-apical and therefore failing to nucleate motile cilia.

The mechanism? Centrioles!
Cilia are anchored to the apical surface of MCCs via 150-200 centrioles, also known as basal bodies. These structures are generated close to the nucleus and then migrate apically, where they dock at the cell surface and subsequently give rise to cilia.

We also performed SEM imaging and observed that ciliary structures are impaired when AK7 is lacking, with reductions in both cilia number and length.

Loss of AK7 was related to PCD-like phenotypes, with decreased fluid flow and reduced beat frequency of MCCs. One of the challenges was to find a way to visualize live ciliary beating with a good enough spatiotemporal resolution (tipically cilia are around 15μm long with beating frequency of 15Hz).

Primary ciliary dyskinesia (PCD) is a condition characterized by impaired mucociliary flow. Mutations in the AK7 gene have been found in patients, but AK7’s role in flow was unclear. We investigated this matter in flow-generating multiciliated cells (MCCs) in the skin epithelium of Xenopus embryos.

This project was definitely a joint effort by multiple people. A huge thank you to all the members of Brian Mitchell’s lab at Northwestern University, and a very special thank you to the other co-first authors, Jennifer Sheridan and Julia Dorr!

Our work suggests that although AK7 localizes at cilia, it has a non-ciliary function too, related to centriole maturation.
We propose that the centriolar defects underlie much of the reduction in cilia number, contributing to the loss of mucociliary flow in AK7-depleted tissues, indicative of PCD.

We observed that AK7 depletion leads to defects in centriole docking, with centrioles remaining sub-apical and therefore failing to nucleate motile cilia.

The mechanism? Centrioles!
Cilia are anchored to the apical surface of MCCs via 150-200 centrioles, also known as basal bodies. These structures are generated close to the nucleus and then migrate apically, where they dock at the cell surface and subsequently give rise to cilia.

We also performed SEM imaging and observed that ciliary structures are impaired when AK7 is lacking, with reductions in both cilia number and length.

Loss of AK7 was related to PCD-like phenotypes, with decreased fluid flow and reduced beat frequency of MCCs. One of the challenges was to find a way to visualize live ciliary beating with a good enough spatiotemporal resolution (tipically cilia are around 15μm long with beating frequency of 15Hz).

Primary ciliary dyskinesia (PCD) is a condition characterized by impaired mucociliary flow. Mutations in the AK7 gene have been found in patients, but AK7’s role in flow was unclear. We investigated this matter in flow-generating multiciliated cells (MCCs) in the skin epithelium of Xenopus embryos.

We tried to cover everything we could - from the overall dynamics of extrusion, to the junction remodeling it requires, until the tissue-scale regulations and its physiological and clinical implications.

…I might be biased, but how fascinating is it to see how much there is still to discover?🤩