A multi-layered and dynamic apical extracellular matrix shapes the vulva lumen in Caenorhabditis elegans

Acceptance summary:

Understanding how cellular tubes are molded and protected by apical extracellular matrices that line their lumens is an extremely interesting question and an exciting research direction.

Decision letter after peer review:

Thank you for submitting your article "A multi-layered and dynamic apical extracellular matrix shapes the vulva lumen in Caenorhabditis elegans" for consideration by eLife. Your article has been reviewed by three peer reviewers, and the evaluation has been overseen by a Reviewing Editor and Piali Sengupta as the Senior Editor. The following individual involved in review of your submission has agreed to reveal their identity: David R Sherwood (Reviewer #1).

The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted this decision to help you prepare a revised submission.

All three reviewers thought the paper made important progress in our understanding of ECM and organogenesis. All three reviewers showed strong enthusiasm towards this manuscript. Their main suggestions for revision is to characterize the loss-of-function mutants or RNAi of VAB-10a, MUP-4 and MUA-3. We look forward to reading the revisions.

We would like to draw your attention to changes in our revision policy that we have made in response to COVID-19 (https://elifesciences.org/articles/57162). Specifically, when editors judge that a submitted work as a whole belongs in eLife but that some conclusions require a modest amount of additional new data, as they do with your paper, we are asking that the manuscript be revised to either limit claims to those supported by data in hand, or to explicitly state that the relevant conclusions require additional supporting data.

Our expectation is that the authors will eventually carry out the additional experiments and report on how they affect the relevant conclusions either in a preprint on bioRxiv or medRxiv, or if appropriate, as a Research Advance in eLife, either of which would be linked to the original paper.

Summary:

In this work, "A multi-layered and dynamic apical extracellular matrix shapes the vulva lumen in Caenorhabditis elegans", the authors use functional fluorescently tagged apical matrix components, confocal microscopy, transmission electron microscopy, and genetics to characterize components and function of apical extracellular matrix (aECM) lining the C. elegans vulval lumen. The authors show that the aECM has distinct elements, including a granular matrix that fills the entire vulval lumen, and central matrix fibrils that form a stalk-like core. The matrix is highly dynamic-its composition varies depending on the developmental stage and the identity of the vulval cells it contacts. Finally, genetic perturbation of vulval matrix components suggest that the matrix is required for proper shaping of the vulval lumen.

Overall, this is an important body of work as it establishes a new and powerful model with many advantages (live imaging, genetics, phenotypic readouts of function) to study poorly understood aECMs during epithelial lumen/tube formation. The work also has a number of important observations, such as how dynamic aECMs are (rapidly assembled and removed), their complex structures (fibrillar and granular components), specific cell type associations, their functions in both constricting and expanding lumens, and functional interactions with the chondroitin proteoglycan luminal matrix. Given the importance of aECMs in epithelial tube formation in vertebrates and invertebrates and the paucity of work examining aECMs, this represents an important advance for the field. Notably, in addition to the aECM, the authors also provide a complete characterization of vulval eversion, which is an overlooked aspect of vulval morphogenesis.

Essential revisions:

1) It would strengthen the manuscript if the authors can determine if a hemi-desmosome-like structures may link the aECM to the vulval cells-intracellular VAB-10a and receptors MUP-4 and MUA-3. We suggest to test if loss of VAB-10a, MUP-4 and MUA-3 result in vulval phenotypes that mirror the aECM loss.

2) Do loss of VAB-10a, MUP-4 and MUA-3 lead to changes in aECM localization?