Decision letter | Egr-5 is a post-mitotic regulator of planarian epidermal differentiation

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Egr-5 is a post-mitotic regulator of planarian epidermal differentiation

Decision letter

Affiliation details

Stowers Institute for Medical Research, United States; Howard Hughes Medical Institute, Stowers Institute for Medical Research, United States
Yukiko M Yamashita, Reviewing editor, University of Michigan, United States

eLife posts the editorial decision letter and author response on a selection of the published articles (subject to the approval of the authors). An edited version of the letter sent to the authors after peer review is shown, indicating the substantive concerns or comments; minor concerns are not usually shown. Reviewers have the opportunity to discuss the decision before the letter is sent (see review process). Similarly, the author response typically shows only responses to the major concerns raised by the reviewers.

Thank you for submitting your work entitled "The planarian epidermis as a model for adult stem cell specification and differentiation" for peer review at eLife. Your submission has been favorably evaluated by Fiona Watt (Senior editor) and three reviewers, one of whom, Yukiko Yamashita, is a member of our Board of Reviewing Editors.

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

The study addresses an important topic of the molecular mechanisms controlling fate transitions among post-mitotic cells. This paper makes a significant contribution to our understanding of epidermal differentiation in planarians. It identifies many useful new markers for characterizing this process, in particular egr-5 as a gene required for maturation of post-mitotic progenitors forming epidermis. The paper is well written, and the data are presented beautifully.

Essential revisions:

1) As the authors point out, other prior work made significant contributions to understanding epidermal differentiation in planarians, and so it is an overstatement to claim (in the Abstract, title, and other locations in the text) that this study establishes the planarian epidermis as a model for studying differentiation. The title in particular should be changed to reflect the precise major contributions this study makes well (implication of egr-5 in control of post-mitotic cell maturation in epidermal differentiation).

2) Need of additional evidence in support of the model that epidermal defects trigger a wound response. At the moment, this great idea is based on the expression of a single marker, delta-1 a known wound-responsive gene. Because the role of delta-1 in the planarian epidermis has not been reported, it is possible that delta could also be activated based on a role it plays in epidermal differentiation. The authors should strengthen this hypothesis by qPCR experiments (or other means) to measure whether other wound-response genes are also upregulated after egr-5 RNAi. Are wound-response genes upregulated in their chd4 and p53 (RNAi) datasets? As there is no functional evidence showing that a loss of epidermal integrity in egr5 RNAi leads to global proliferation/apoptosis, in parallel to conducting some of the critical and feasible experiments. We also recommend toning down the language, if necessary, depending on how much the claim can be strengthened with additional experiments that are feasible and within the scope of revision.

3) Lineage hierarchy described in Figure 8 is not entirely supported by the experimental data. There are a few straightforward experiments that can be done to strengthen this model. Also, the authors could soften the conclusion where the straightforward experiments are not possible. Several examples of possible experiments: Does zfp-1 RNAi reduce zpuf-6 and vim-3 expression? How does the zfp-1 RNAi RNA-seq dataset compare with the p53 RNAi and chd4 RNAi datasets (were egr-5 and zpuf-6 previously identified in that dataset)? What is the phenotype of zpuf-6 RNAi animals? Do egr-5 RNAi animals lose or fail to form nb22.12e/laminB-expressing cells?