FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis

Thank you for sending your work entitled “FBN-1 is required for resistance of the epidermis to mechanical deformation during C. elegans embryonic development” for consideration at eLife. Your article has been favorably evaluated by Janet Rossant (Senior editor) and three reviewers, one of whom is a member of our Board of Reviewing Editors.

The Reviewing editor and the other reviewers discussed their comments before we reached this decision, and the Reviewing editor has assembled the following comments to help you prepare a revised submission.

Morphogenesis involves the generation and correct localization of forces. Although many molecules known to be required for morphogenesis are known, our understanding of how they function and their relationship with force is limited. Using genetic, phenotypic analyses, and a FRET-based tension sensor, the authors identify and characterize a mechanical force that occurs during development of the C. elegans mouth and show that FBN-1 plays a role in resisting this inward pulling force. They also identify genes required for proper fbn-1 expression. This is an interesting overall study that advances our understanding of the processes and factors controlling morphogenetic movements and should be of wide interest.

Points that need to be addressed:

1) The experiments with the three control FRET sensors are important validations of the FRET sensor. Details of their construction should be included in the Methods. Also, do the control UNC-70 sensors UNC-70(TRAF) and UNC-70(5aa) rescue unc-70 mutants as the FRET sensor does? This is an important validation of the control sensors.

2) How regions outside the sensory depression were chosen for measurement in the FRET experiments is not clear from the Methods. The authors said that they selected an ROI over the putative pharynx attachment site and another ROI “over the rest of the embryo.” The Results section says that pixels with similar expression levels were chosen. Were the ROIs the same size? Where in the embryo were the chosen non-sensory depression ROIs? How were they chosen?

3) There are some concerns regarding interpretation of the force sensor data. The authors record molecular tension, which cannot necessarily be translated into tissue tension given that the molecular machinery transmitting forces within and between tissues are not entirely known. In the absence of experiments testing mechanical resistance of the embryonic sheath, the authors should more clearly describe the limitations of the force sensor data for supporting their mechanical model.