PCOMPBIOL-D-25-01098

Start Small: A Model for Tissue-wide Planar Cell Polarity without Morphogens

PLOS Computational Biology

Dear Dr. Belmonte,

Thank you very much for submitting your manuscript to PLOS Computational Biology. After careful consideration, the reviewers felt that the manuscript presents an exciting extension of PCP modeling with potentially broad interest but there are several outstanding questions for the manuscript to fully meet PLOS Computational Biology's publication criteria. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. We look forward to your revised submission!

Please submit your revised manuscript within 60 days Sep 16 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at ploscompbiol@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pcompbiol/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

* A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to formatting updates and technical items listed in the 'Journal Requirements' section below.

* A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

* An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter

We look forward to receiving your revised manuscript.

Kind regards,

Calina Copos, Ph.D.

Academic Editor

PLOS Computational Biology

Marc Birtwistle

Section Editor

PLOS Computational Biology

Additional Editor Comments :

A couple reviewers have pointed out that the simulation code is provided but the simulation output or analysis code are not. Please ensure these are provided in the revised version.

Journal Requirements:

1) Please ensure that the CRediT author contributions listed for every co-author are completed accurately and in full.

At this stage, the following Authors/Authors require contributions: Abhisha Thayambath, and Julio M Belmonte. Please ensure that the full contributions of each author are acknowledged in the "Add/Edit/Remove Authors" section of our submission form.

The list of CRediT author contributions may be found here: https://journals.plos.org/ploscompbiol/s/authorship#loc-author-contributions

2) We ask that a manuscript source file is provided at Revision. Please upload your manuscript file as a .doc, .docx, .rtf or .tex. If you are providing a .tex file, please upload it under the item type u2018LaTeX Source Fileu2019 and leave your .pdf version as the item type u2018Manuscriptu2019.

3) Please provide an Author Summary. This should appear in your manuscript between the Abstract (if applicable) and the Introduction, and should be 150-200 words long. The aim should be to make your findings accessible to a wide audience that includes both scientists and non-scientists. Sample summaries can be found on our website under Submission Guidelines:

https://journals.plos.org/ploscompbiol/s/submission-guidelines#loc-parts-of-a-submission

4) Please upload all main figures as separate Figure files in .tif or .eps format. For more information about how to convert and format your figure files please see our guidelines:

https://journals.plos.org/ploscompbiol/s/figures

5) We have noticed that you have uploaded Supporting Information files, but you have not included a list of legends. Please add a full list of legends for your Supporting Information files after the references list.

6) Some material included in your submission may be copyrighted. According to PLOSu2019s copyright policy, authors who use figures or other material (e.g., graphics, clipart, maps) from another author or copyright holder must demonstrate or obtain permission to publish this material under the Creative Commons Attribution 4.0 International (CC BY 4.0) License used by PLOS journals. Please closely review the details of PLOSu2019s copyright requirements here: PLOS Licenses and Copyright. If you need to request permissions from a copyright holder, you may use PLOS's Copyright Content Permission form.

Please respond directly to this email and provide any known details concerning your material's license terms and permissions required for reuse, even if you have not yet obtained copyright permissions or are unsure of your material's copyright compatibility. Once you have responded and addressed all other outstanding technical requirements, you may resubmit your manuscript within Editorial Manager.

Potential Copyright Issues:

i) Figure 1. Thank you for stating "Panel A adapted from [17]". Please provide written permission from the copyright holder to publish this under our CC-BY 4.0 license, or remove the figure / replace the image. Please note we do not recommend using standard request forms available on Publishers' websites, as they grant single use rather than republication under an open access license.

7) Thank you for stating "The simulation code ispublicly available at https://github.com/abhisha-ramesh/PCP Subcellular Potts Model." This link reaches a 404 error page. Please amend this to a working link and update your Data Availability Statement in the online submission form accordingly.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Authors:

Please note that one of the reviews is uploaded as an attachment.

Reviewer #1: A long-standing question in polarity field is how long-range polarity is established and whether morphogen gradients are required. This paper describes a new computational model of planar cell polarity (PCP) that lacks long-range cues, which have been shown to be required in most other theoretical models of PCP. Using a Cellular Potts framework and modeling the partitioning of proximal-distal compartments using differential adhesion of opposing complexes within and between cells, the authors show that this can give rise to spontaneous polarization with strong local alignment in small tissues. However, larger tissues lack long-range alignment without a directional cue, even when an orientation boundary is provided, giving rise to high local order but little global alignment (swirling patterns), as observed in prior models. Coupling a polarizing boundary in a small field of cells that is allowed to grow with uniform proliferation results in robust large-scale polarization, as daughters cells will repolarize utilizing cues from their neighbors. This work nicely demonstrates that a small tissue adjacent to a polarizing boundary can establish long-range polarization if coupled with cell proliferation, as was previously proposed in vivo in the Drosophila larval wing (Sagner et al, 2012).

Although there are many theoretical models for PCP, the current phenomenological model is distinct in its use of the Cellular Potts framework, and by incorporating growth and proliferation as a mechanism to propagate/expand existing polarization. This is exciting because it points experimentalists searching for the elusive global cue for PCP in a new direction, suggesting that an edge or a boundary, rather than a graded morphogen, may be sufficient especially if polarization is established when the tissue is small. These findings will be of broad interest to those interested in tissue patterning and cell polarity.

I have some comments that would improve the readability of the manuscript.

1. In Figure 2A, the model is described as continuous so that all cells had one junction. But I assume this was not implemented for cases involving a boundary (Fig. 2B) or leading edge expansion. Needs clarification.

2. Given that a ‘distal’ orienting bounding is sufficient to generate aligned polarity in small tissues with growth, I wondered what would happen if the polarization boundary was of ‘lateral compartment’ character. Does this provide any bias to align polarity w/ or w/out cell division? In the mouse skin, polarity initiates from the midline outward (Aw et al 2016).

3. Figure 3 shows the model with leading edge divisions is less successful in propagating polarity compared to uniform divisions. I wondered why this condition was tested in the first place. Are there example of tissues that grow in this way? Perhaps during wound repair or limb outgrowth? Other aspects/assumptions of the model (repolarization during division) are rooted in experimental observations, so it would be helpful to place leading edge divisions in a physiological context as well.

4. Figure S4 plots the minor versus random axis division impact on polarization in the uniform or leading-edge division models. The minor axis had small (~3%) improvement over the random axis. Firstly, the long axis is never explicitly tested and secondly, I think the statement above is too strong for such small improvement.

5. Some of the language related to division orientation is confusing to an experimentalist. Division orientation typically refers to spindle orientation ie, according to Hertwig’s rule, cells divide with the spindle aligned with the cell’s long axis. The cleavage plane is therefore aligned with the short/minor axis. In the discussion, “division along the long axis results in daughter cells maintaining more surface contact with each other than with external neighbours, reducing their access to external polarity cues and leading to weaker polarization.” I think if the authors use the terms ‘spindle alignment’ and ‘cleavage plane’ to describe their data, this will be more accessible to experimentalists.

6. In the discussion, the authors explain why they chose model parameters that allow cell autonomous polarization, but state that other parameters that prevent cell-autonomous polarization are also effective in generating long-range polarization. It would be useful to include these data as a supplementary figure.

7. Figure S1B/C, S5 and TableS1 are not referred to in the text.

Reviewer #2: SUMMARY :

The paper revisits the self-organization problem of Planar cell polarity, PCP, the alignment of cell polarity along epithelial sheets that underlies several morphodynamic processes in vertebrates. Whereas several key molecular pathways have been uncovered over the years and several computational models have shown that local cell-cell interactions can explain self-organization on a local scale, most models to date have required a global cue to explain patterning across large tissues. However, experimental efforts to uncover said global cue have not succeeded so far, raising the question if such a global cue truly exists.

In this work, the authors build a cellular Potts model in which PCP emerges without the need for a global polarity cue, through a combination of local symmetry breaking followed by symmetry maintenance during a proliferative process.

The model is nice because it is the first to show spontaneous emergence of PCP in larger systems without the presence of a global cue, and several interesting analyses are performed throughout the paper. As such, the paper has the potential to be a valuable contribution to the field. However, I do have some open questions that I think should be addressed before publication.

QUESTIONS / COMMENTS :

(1) It was not immediately clear to me what exactly the motivation for some of the experiments and the overall work was. This actually became much clearer when reading the discussion:

1a) for example on P12 : “While the mechanisms of local planar cell polarity …. All these negative results suggest that an alternative mechanism, independent of morphogen gradients, may be required to establish global PCP orientation.” I feel like this captures the essence of the paper quite clearly and concisely – but for me, this message got a bit lost in the introduction, likely because of the amount of detail given about the underlying molecular mechanisms (details which do not seem to be used throughout the paper. My suggestion would be to swap these parts: the discussion paragraph above is ideal for the problem statement in the introduction because it is quite conceptual. The discussion could then go into more detail about how this now ties in with known molecular mechanisms and what it might mean for that field.

1b) The same holds for the motivation for the experiments with different boundary conditions in Fig2, as it was not clear to me what the biological motivation for these experiments was – until the discussion on p12 “Sanger et al proposed that PCP may be established early in development, while the tissue is still small, with the guidance of local boundary signals, and long-range tissue orientation arises through subsequent cell proliferation”. This motivation should ideally provided in the introduction and/or in the results section where these experiments are performed.

1c) The discussion nicely places the results in context of literature. But I would also like to see some ideas on how this model could now be experimentally tested, and how (if at all) it differs in behavior from existing models with global polarity cue. It is nice that this model explains the data without the need for this global polarity cue, but that still does not guarantee that this is the “correct” model. That is fine, but it would be good if the discussion can provide further directions on how to continue from here.

(2) Not all parameter values are described: what is T? What is lambda_V? What is V_t? What is the field size? To ensure the work is reproducible, these details should be added.

(3) P8 “We found that as the number of cells increases, global polarization decreases in both configurations (Fig 3A).” and P10 “This clearly suggests that when the system size increases, there is no long-range order across the entire system in the absence of a directional cue”.

3a) I am not sure this is fair since the time it takes to reach the ordered state also increases (maybe even exponentially?) with system size. From Fig S1C it is clear that the larger systems have not yet plateaued at the maximum simulation time. So from this it is not clear whether it is fundamentally impossible to achieve the global ordering, or that it just takes (much) longer. I think it would be useful to complement this analysis with “time taken until a certain amount of ordering is reached” – e.g. the time it takes to reach phi = 0.5, to give you a sense of how the required time scales with system size.

3b) Related: it would be useful to give some indication of how the CPM time in MCS could be related to real time, if possible. For example, is it known how fast individual cells can reorient, and could you use this to set/estimate this scaling from Fig S1A? And if you do, could you compare the predicted ordering time to some experimental data? (Not perfectly, just in terms of order of magnitude to begin with)? Likewise , is the doubling time then realistic?

(4) The paper occasionally seems to conflate two concepts: emergence of order from disorder, and maintenance of order that is already there. For example P10 “This suggests that the distance over which the polarity alignment is maintained, the correlation length, is very small” and “This indicates that the boundary signal helps maintain the cell polarity”. But these experiments all focus on emergence of the order from an unordered system. Since the time to reach the ordered state also increases rapidly with system size (Fig S1C), this does not allow you to ask the second interesting question: what is the max amount of ordering the system can maintain? For that, I think it would be interesting to do a complementary experiment where the cells are initialized in the ordered state, and you evaluate over what spatial scale this ordering is maintained over time.

(5) P5 “We determined the exact values for each contact energy term by extensive parameter scans aimed at optimizing polarization for small systems.” It would be good if the authors could show the results of that parameter scan. How wide/narrow is the regime where this polarization occurs? Are results in the paper expected to hold across different local polarization parameter scenarios?

(6) P8 “The addition of this boundary signal not only biases the global alignment direction but also enhances the global polarization compared to the periodic boundary configuration for nearly all time steps in the simulation (Figure 2D)”.

6a ) Could this be because the leftmost column of cells has a different shape and (potentially) a less variable, high phi? I think it would be worthwhile to check if this still holds when only considering the middle two columns of cells, which are more comparable in shape between the two scenarios.

6b ) Related: there is of course some anisotropy because this is a lattice-based model, which also has implications for the sides of the (hexagonal) cells. Does the left boundary signal scenario in Fig 2B still give the same 4 outputs as in Fig 2A? To what extent is the distribution of order parameter values (say at the final timestep) similar between the 4 potential output directions shown in Fig 2A? If you put the boundary at an angle, do the results still hold?

(7) P12 “we observe that the alignment is not strictly along the x-axis but instead shifts towards +/- 60 degrees”

7a ) I find this somewhat suspicious because this would correspond to the sides of the hexagonal cell shape. Is there any way to check if this is a “real” result or if anisotropy is at play here? What if you placed the boundary signal at an angle?

7b) Related on p13 “We believe that the directional shift in polarity alignment observed for cell proliferation on the front scenario could be due to the lack of ability of the newly divided cells at the boundary to fully integrate polarity cues from all directions”. Interesting hypothesis, but could you test this further with some exps/further analysis? E.g. testing how cells polarize when surrounded by varying numbers of cells, but you may be able to come up with other experiments as well.

(8) P12 “Results remain the same for slower growth rates, but polarization is gradually lost for faster growth rates, suggesting that cells need some time to adjust their polarity before the next round of division to maintain local tissue alignment (Fig S6)”. Could you further support this hypothesis by comparing the distribution of “time between divisions” to that of “time taken by a single cell to (re)polarize”?

(9) P13 “We chose our model parameters (see Table 2) to reflect the latter case; however, setting the internal contact energies to negative values to prevent cell-autonomous polarization still allows spontaneous tissue polarization, and the key results from our model remain qualitatively the same”. That is nice to hear – but ideally, these results should also be shown in the paper and/or supplement.

MINOR COMMENTS TO THE AUTHOR (no response required):

- P3 “However, all these models are based either on a pre-established PCP order from which the applied tension realigns the orientation or on a specific sequence of PCP activation of cell rows that facilitates global tissue alignment”. What is meant by “sequence of PCP activation of cell rows”? Please clarify.

- Tables 1 and 2: does this imply that the adhesion energies are asymmetric, or do you simply report as a diagonal matrix to avoid duplicate values? Please clarify.

- P3 “Within each cell, these compartments exhibit low affinity for each other, leading to their spatial segregation” – I think in the CPM this would be better described as “actively repel” each other than “have low affinity”, as the latter (neutral adhesion values) would probably not lead to segregation.

- P4 “formed by a collection of lattice sites on a square or hexagonal grid in 2D or 3D. In this work, I assume it is only 2D square? If yes, this should perhaps be mentioned here.

- Fig 1 phi = 0, phi = 1 – I assume these are not the measured values? Consider replacing either with the measured values or phi ~ 0, phi ~ 1 (i.e. replace "=" with "approximate =")

- Fig 1B’ what does the blue box mean?

- Fig 2A what does the red box mean?

- Fig 2C is this the distribution of individual cell angles within a simulation, or of mean cell angles between the 100 simulations?

- Fig 2D can you give an indication of the robustness of this order parameter across simulations? Plot shows the mean, but what is the SD/standard error?

- What boundary conditions were used in Figs 2E/2E’?

- Fig 2A,2B: text refers to “a system of 8 x 8 cells” but the figures show 4 x 4.

Reviewer #3: Attached

**********

Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data and code should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: None

Reviewer #2: Yes

Reviewer #3: None

**********

PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

Figure resubmission:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. If there are other versions of figure files still present in your submission file inventory at resubmission, please replace them with the PACE-processed versions.

Reproducibility:

To enhance the reproducibility of your results, we recommend that authors of applicable studies deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Attachments

Attachment

Submitted filename: Thayambath PCP morphogen report.pdf

PCOMPBIOL-D-25-01098R1

Start Small: A Model for Tissue-wide Planar Cell Polarity without Morphogens

PLOS Computational Biology

Dear Dr. Belmonte,

Thank you for addressing the comments of the three reviewers in great detail. All of them appreciated your work in editing the manuscript. We would like to accept the manuscript but one reviewer asked for two points to be addressed. Therefore, we invite you to submit a revised version addressing these two points for a final editorial review process.

Please submit your revised manuscript by Jan 26 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at ploscompbiol@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pcompbiol/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

* A rebuttal letter that responds to each point raised by Reviewer #2. You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to formatting updates and technical items listed in the 'Journal Requirements' section below.

* A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

* An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Calina Copos, Ph.D.

Academic Editor

PLOS Computational Biology

Marc Birtwistle

Section Editor

PLOS Computational Biology

Journal Requirements:

1) Please ensure that the CRediT author contributions listed for every co-author are completed accurately and in full.

At this stage, the following Authors/Authors require contributions: Abhisha Thayambath, and Julio M Belmonte. Please ensure that the full contributions of each author are acknowledged in the "Add/Edit/Remove Authors" section of our submission form.

The list of CRediT author contributions may be found here: https://journals.plos.org/ploscompbiol/s/authorship#loc-author-contributions

2) We note that your Supplementary Figures files are duplicated on your submission as they are included in supplementary.pdf and SupplFigures.zip files. Please remove any unnecessary or old files from your revision, and make sure that only those relevant to the current version of the manuscript are included.

Note: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Reviewers' comments:

Reviewer's Responses to Questions

Reviewer #1: The authors have done an excellent job responding to reviewers comments and suggestions. The addition of a new section comparing autonomous vs non-autonomous PCP mechanisms is timely and strengthens the paper. The additional context and model predictions added to the discussion also improve readability. Overall this is a valuable and well executed study that with have substantial impact on the polarity field.

Reviewer #2: I appreciate the care taken in addressing the reviewer comments, which has greatly improved the manuscript.

I have only two remaining (relatively minor) comments:

- It seems as if many of the newly added supplementary figures are only mentioned the first time in the discussion, which reads a bit odd given that the discussion is normally not intended to present new data. I would suggest to integrate these with the results section.

- RE setting the time scale of the CPM: I understand the author's comment that this is difficult because no experimental measurement of polarization time is available, so I'll leave the choice up to them. However, one of the other reviewers mentioned the same issue so I think it might be worth making an attempt. I think that even if polarization time is not experimentally measured, it is probably possible to provide a (very rough!) estimate of at least the order of magnitude of this polarization time. Even if you still measure time in MCS, you could then at least test in what order of magnitude the tissue polarization time would end up , and to what extent that is realistic - I don't think the estimate needs to be perfect to give at least *some* indication that would massively help with interpretation here and as such improve the paper's impact. However, given the large amount of additional work the authors already did, I'll leave the choice up to them (it's not strictly necessary for the paper but would make it stronger if possible).

Reviewer #3: The revision is adequate

**********

Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data and code should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: None

**********

PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

Figure resubmission:

While revising your submission, we strongly recommend that you use PLOS’s NAAS tool (https://ngplosjournals.pagemajik.ai/artanalysis) to test your figure files. NAAS can convert your figure files to the TIFF file type and meet basic requirements (such as print size, resolution), or provide you with a report on issues that do not meet our requirements and that NAAS cannot fix.

After uploading your figures to PLOS’s NAAS tool - https://ngplosjournals.pagemajik.ai/artanalysis, NAAS will process the files provided and display the results in the "Uploaded Files" section of the page as the processing is complete. If the uploaded figures meet our requirements (or NAAS is able to fix the files to meet our requirements), the figure will be marked as "fixed" above. If NAAS is unable to fix the files, a red "failed" label will appear above. When NAAS has confirmed that the figure files meet our requirements, please download the file via the download option, and include these NAAS processed figure files when submitting your revised manuscript.

Reproducibility:

To enhance the reproducibility of your results, we recommend that authors of applicable studies deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Dear Dr Belmonte,

We are pleased to inform you that your manuscript 'Start Small: A Model for Tissue-wide Planar Cell Polarity without Morphogens' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology.

Best regards,

Calina Copos, Ph.D.

Academic Editor

PLOS Computational Biology

Marc Birtwistle

Section Editor

PLOS Computational Biology

***********************************************************