--- _id: '13081' abstract: - lang: eng text: During development, tissues undergo changes in size and shape to form functional organs. Distinct cellular processes such as cell division and cell rearrangements underlie tissue morphogenesis. Yet how the distinct processes are controlled and coordinated, and how they contribute to morphogenesis is poorly understood. In our study, we addressed these questions using the developing mouse neural tube. This epithelial organ transforms from a flat epithelial sheet to an epithelial tube while increasing in size and undergoing morpho-gen-mediated patterning. The extent and mechanism of neural progenitor rearrangement within the developing mouse neuroepithelium is unknown. To investigate this, we per-formed high resolution lineage tracing analysis to quantify the extent of epithelial rear-rangement at different stages of neural tube development. We quantitatively described the relationship between apical cell size with cell cycle dependent interkinetic nuclear migra-tions (IKNM) and performed high cellular resolution live imaging of the neuroepithelium to study the dynamics of junctional remodeling. Furthermore, developed a vertex model of the neuroepithelium to investigate the quantitative contribution of cell proliferation, cell differentiation and mechanical properties to the epithelial rearrangement dynamics and validated the model predictions through functional experiments. Our analysis revealed that at early developmental stages, the apical cell area kinetics driven by IKNM induce high lev-els of cell rearrangements in a regime of high junctional tension and contractility. After E9.5, there is a sharp decline in the extent of cell rearrangements, suggesting that the epi-thelium transitions from a fluid-like to a solid-like state. We found that this transition is regulated by the growth rate of the tissue, rather than by changes in cell-cell adhesion and contractile forces. Overall, our study provides a quantitative description of the relationship between tissue growth, cell cycle dynamics, epithelia rearrangements and the emergent tissue material properties, and novel insights on how epithelial cell dynamics influences tissue morphogenesis. acknowledged_ssus: - _id: Bio - _id: LifeSc alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Laura full_name: Bocanegra, Laura id: 4896F754-F248-11E8-B48F-1D18A9856A87 last_name: Bocanegra citation: ama: Bocanegra L. Epithelial dynamics during mouse neural tube development. 2023. doi:10.15479/at:ista:13081 apa: Bocanegra, L. (2023). Epithelial dynamics during mouse neural tube development. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:13081 chicago: Bocanegra, Laura. “Epithelial Dynamics during Mouse Neural Tube Development.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13081. ieee: L. Bocanegra, “Epithelial dynamics during mouse neural tube development,” Institute of Science and Technology Austria, 2023. ista: Bocanegra L. 2023. Epithelial dynamics during mouse neural tube development. Institute of Science and Technology Austria. mla: Bocanegra, Laura. Epithelial Dynamics during Mouse Neural Tube Development. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:13081. short: L. Bocanegra, Epithelial Dynamics during Mouse Neural Tube Development, Institute of Science and Technology Austria, 2023. date_created: 2023-05-23T19:10:42Z date_published: 2023-05-23T00:00:00Z date_updated: 2023-10-04T11:14:04Z day: '23' ddc: - '570' degree_awarded: PhD department: - _id: GradSch - _id: AnKi doi: 10.15479/at:ista:13081 file: - access_level: closed checksum: 74f3f89e59a0189bee53ebfad9c1b9af content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: lbocaneg date_created: 2023-05-25T06:32:12Z date_updated: 2023-05-25T06:32:12Z file_id: '13089' file_name: Thesis_final_LauraBocanegra.docx file_size: 25615534 relation: source_file - access_level: closed checksum: c6cdef6323eacfb4b7a8af20f32eae97 content_type: application/pdf creator: lbocaneg date_created: 2023-05-25T06:32:16Z date_updated: 2023-05-25T06:32:16Z embargo: 2024-05-31 embargo_to: open_access file_id: '13090' file_name: TotalFinal_Thesis_LauraBocanegraArx.pdf file_size: 12386046 relation: main_file file_date_updated: 2023-05-25T06:32:16Z has_accepted_license: '1' language: - iso: eng license: https://creativecommons.org/licenses/by-nc-nd/4.0/ month: '05' oa_version: Published Version page: '93' publication_identifier: issn: - 2663 - 337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '9349' relation: part_of_dissertation status: public - id: '12837' relation: part_of_dissertation status: public status: public supervisor: - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 title: Epithelial dynamics during mouse neural tube development tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: dissertation user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9 year: '2023' ... --- _id: '12837' abstract: - lang: eng text: As developing tissues grow in size and undergo morphogenetic changes, their material properties may be altered. Such changes result from tension dynamics at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms controlling the physical state of growing tissues are unclear. We found that at early developmental stages, the epithelium in the developing mouse spinal cord maintains both high junctional tension and high fluidity. This is achieved via a mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the cell proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification uncovered here resembles a glass transition that depends on the dynamical stresses generated by proliferation and differentiation. Our finding that the fluidity of developing epithelia is linked to interkinetic nuclear movements and the dynamics of growth is likely to be relevant to multiple developing tissues. acknowledgement: 'We thank S. Hippenmeyer for the reagents and C. P. Heisenberg, J. Briscoe and K. Page for comments on the manuscript. This work was supported by IST Austria; the European Research Council under Horizon 2020 research and innovation programme grant no. 680037 and Horizon Europe grant 101044579 (A.K.); Austrian Science Fund (FWF): F78 (Stem Cell Modulation) (A.K.); ISTFELLOW postdoctoral program (A.S.); Narodowe Centrum Nauki, Poland SONATA, 2017/26/D/NZ2/00454 (M.Z.); and the Polish National Agency for Academic Exchange (M.Z.).' article_processing_charge: No article_type: original author: - first_name: Laura full_name: Bocanegra, Laura id: 4896F754-F248-11E8-B48F-1D18A9856A87 last_name: Bocanegra - first_name: Amrita full_name: Singh, Amrita id: 76250f9f-3a21-11eb-9a80-a6180a0d7958 last_name: Singh - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Marcin P full_name: Zagórski, Marcin P id: 343DA0DC-F248-11E8-B48F-1D18A9856A87 last_name: Zagórski orcid: 0000-0001-7896-7762 - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 citation: ama: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. 2023;19:1050-1058. doi:10.1038/s41567-023-01977-w apa: Bocanegra, L., Singh, A., Hannezo, E. B., Zagórski, M. P., & Kicheva, A. (2023). Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-023-01977-w chicago: Bocanegra, Laura, Amrita Singh, Edouard B Hannezo, Marcin P Zagórski, and Anna Kicheva. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” Nature Physics. Springer Nature, 2023. https://doi.org/10.1038/s41567-023-01977-w. ieee: L. Bocanegra, A. Singh, E. B. Hannezo, M. P. Zagórski, and A. Kicheva, “Cell cycle dynamics control fluidity of the developing mouse neuroepithelium,” Nature Physics, vol. 19. Springer Nature, pp. 1050–1058, 2023. ista: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. 2023. Cell cycle dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics. 19, 1050–1058. mla: Bocanegra, Laura, et al. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.” Nature Physics, vol. 19, Springer Nature, 2023, pp. 1050–58, doi:10.1038/s41567-023-01977-w. short: L. Bocanegra, A. Singh, E.B. Hannezo, M.P. Zagórski, A. Kicheva, Nature Physics 19 (2023) 1050–1058. date_created: 2023-04-16T22:01:09Z date_published: 2023-07-01T00:00:00Z date_updated: 2023-10-04T11:14:05Z day: '01' ddc: - '570' department: - _id: EdHa - _id: AnKi doi: 10.1038/s41567-023-01977-w ec_funded: 1 external_id: isi: - '000964029300003' file: - access_level: open_access checksum: 858225a4205b74406e5045006cdd853f content_type: application/pdf creator: dernst date_created: 2023-10-04T11:13:28Z date_updated: 2023-10-04T11:13:28Z file_id: '14392' file_name: 2023_NaturePhysics_Boncanegra.pdf file_size: 5532285 relation: main_file success: 1 file_date_updated: 2023-10-04T11:13:28Z has_accepted_license: '1' intvolume: ' 19' isi: 1 language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '07' oa: 1 oa_version: Published Version page: 1050-1058 project: - _id: B6FC0238-B512-11E9-945C-1524E6697425 call_identifier: H2020 grant_number: '680037' name: Coordination of Patterning And Growth In the Spinal Cord - _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa grant_number: '101044579' name: Mechanisms of tissue size regulation in spinal cord development - _id: 059DF620-7A3F-11EA-A408-12923DDC885E grant_number: F07802 name: Morphogen control of growth and pattern in the spinal cord - _id: 25681D80-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '291734' name: International IST Postdoc Fellowship Programme publication: Nature Physics publication_identifier: eissn: - 1745-2481 issn: - 1745-2473 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: record: - id: '13081' relation: dissertation_contains status: public scopus_import: '1' status: public title: Cell cycle dynamics control fluidity of the developing mouse neuroepithelium tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 19 year: '2023' ... --- _id: '9349' abstract: - lang: eng text: 'The way in which interactions between mechanics and biochemistry lead to the emergence of complex cell and tissue organization is an old question that has recently attracted renewed interest from biologists, physicists, mathematicians and computer scientists. Rapid advances in optical physics, microscopy and computational image analysis have greatly enhanced our ability to observe and quantify spatiotemporal patterns of signalling, force generation, deformation, and flow in living cells and tissues. Powerful new tools for genetic, biophysical and optogenetic manipulation are allowing us to perturb the underlying machinery that generates these patterns in increasingly sophisticated ways. Rapid advances in theory and computing have made it possible to construct predictive models that describe how cell and tissue organization and dynamics emerge from the local coupling of biochemistry and mechanics. Together, these advances have opened up a wealth of new opportunities to explore how mechanochemical patterning shapes organismal development. In this roadmap, we present a series of forward-looking case studies on mechanochemical patterning in development, written by scientists working at the interface between the physical and biological sciences, and covering a wide range of spatial and temporal scales, organisms, and modes of development. Together, these contributions highlight the many ways in which the dynamic coupling of mechanics and biochemistry shapes biological dynamics: from mechanoenzymes that sense force to tune their activity and motor output, to collectives of cells in tissues that flow and redistribute biochemical signals during development.' acknowledgement: The AK group is supported by IST Austria and by the ERC under European Union Horizon 2020 research and innovation programme Grant 680037. Apologies to those whose work could not be mentioned due to limited space. We thank all my lab members, both past and present, for stimulating discussion. This work was funded by a Singapore Ministry of Education Tier 3 Grant, MOE2016-T3-1-005. We thank Francis Corson for continuous discussion and collaboration contributing to these views and for figure 4(A). PC is sponsored by the Institut Pasteur and the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No. 665807. Research in JG's laboratory is funded by the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement No. 337635, Institut Pasteur, CNRS, Cercle FSER, Fondation pour la Recherche Medicale, the Vallee Foundation and the ANR-19-CE-13-0024 Grant. We thank Erez Braun and Alex Mogilner for comments on the manuscript and Niv Ierushalmi for help with figure 5. This project has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. ERC-2018-COG Grant 819174-HydraMechanics awarded to KK. EH thanks all lab members, as well as Pierre Recho, Tsuyoshi Hirashima, Diana Pinheiro and Carl-Philip Heisenberg, for fruitful discussions on these topics—and apologize for not being able to cite many very relevant publications due to the strict 10-reference limit. EH acknowledges the support of Austrian Science Fund (FWF) (P 31639) and the European Research Council under the European Union's Horizon 2020 Research and Innovation Programme Grant Agreements (851288). The authors acknowledge the inspiring scientists whose work could not be cited in this perspective due to space constraints; the members of the Gartner Lab for helpful discussions; the Barbara and Gerson Bakar Foundation, the Chan Zuckerberg Biohub Investigators Programme, the National Institute of Health, and the Centre for Cellular Construction, an NSF Science and Technology Centre. The Minc laboratory is currently funded by the CNRS and the European Research Council (CoG Forcaster No. 647073). Research in the lab of J-LM is supported by the Institut Curie, the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé Et de la Recherche Médicale (INSERM), and is funded by grants from the ATIP-Avenir programme, the Fondation Schlumberger pour l'Éducation et la Recherche via the Fondation pour la Recherche Médicale, the European Research Council Starting Grant ERC-2017-StG 757557, the European Molecular Biology Organization Young Investigator programme (EMBO YIP), the INSERM transversal programme Human Development Cell Atlas (HuDeCA), Paris Sciences Lettres (PSL) 'nouvelle équipe' and QLife (17-CONV-0005) grants and Labex DEEP (ANR-11-LABX-0044) which are part of the IDEX PSL (ANR-10-IDEX-0001-02). We acknowledge useful discussions with Massimo Vergassola, Sebastian Streichan and my lab members. Work in my laboratory on Drosophila embryogenesis is partly supported by NIH-R01GM122936. The authors acknowledge the support by a grant from the European Research Council (Grant No. 682161). Lenne group is funded by a grant from the 'Investissements d'Avenir' French Government programme managed by the French National Research Agency (ANR-16-CONV-0001) and by the Excellence Initiative of Aix-Marseille University—A*MIDEX, and ANR projects MechaResp (ANR-17-CE13-0032) and AdGastrulo (ANR-19-CE13-0022). article_number: '041501' article_processing_charge: No article_type: original author: - first_name: Pierre François full_name: Lenne, Pierre François last_name: Lenne - first_name: Edwin full_name: Munro, Edwin last_name: Munro - first_name: Idse full_name: Heemskerk, Idse last_name: Heemskerk - first_name: Aryeh full_name: Warmflash, Aryeh last_name: Warmflash - first_name: Laura full_name: Bocanegra, Laura id: 4896F754-F248-11E8-B48F-1D18A9856A87 last_name: Bocanegra - first_name: Kasumi full_name: Kishi, Kasumi id: 3065DFC4-F248-11E8-B48F-1D18A9856A87 last_name: Kishi - first_name: Anna full_name: Kicheva, Anna id: 3959A2A0-F248-11E8-B48F-1D18A9856A87 last_name: Kicheva orcid: 0000-0003-4509-4998 - first_name: Yuchen full_name: Long, Yuchen last_name: Long - first_name: Antoine full_name: Fruleux, Antoine last_name: Fruleux - first_name: Arezki full_name: Boudaoud, Arezki last_name: Boudaoud - first_name: Timothy E. full_name: Saunders, Timothy E. last_name: Saunders - first_name: Paolo full_name: Caldarelli, Paolo last_name: Caldarelli - first_name: Arthur full_name: Michaut, Arthur last_name: Michaut - first_name: Jerome full_name: Gros, Jerome last_name: Gros - first_name: Yonit full_name: Maroudas-Sacks, Yonit last_name: Maroudas-Sacks - first_name: Kinneret full_name: Keren, Kinneret last_name: Keren - first_name: Edouard B full_name: Hannezo, Edouard B id: 3A9DB764-F248-11E8-B48F-1D18A9856A87 last_name: Hannezo orcid: 0000-0001-6005-1561 - first_name: Zev J. full_name: Gartner, Zev J. last_name: Gartner - first_name: Benjamin full_name: Stormo, Benjamin last_name: Stormo - first_name: Amy full_name: Gladfelter, Amy last_name: Gladfelter - first_name: Alan full_name: Rodrigues, Alan last_name: Rodrigues - first_name: Amy full_name: Shyer, Amy last_name: Shyer - first_name: Nicolas full_name: Minc, Nicolas last_name: Minc - first_name: Jean Léon full_name: Maître, Jean Léon last_name: Maître - first_name: Stefano full_name: Di Talia, Stefano last_name: Di Talia - first_name: Bassma full_name: Khamaisi, Bassma last_name: Khamaisi - first_name: David full_name: Sprinzak, David last_name: Sprinzak - first_name: Sham full_name: Tlili, Sham last_name: Tlili citation: ama: Lenne PF, Munro E, Heemskerk I, et al. Roadmap for the multiscale coupling of biochemical and mechanical signals during development. Physical biology. 2021;18(4). doi:10.1088/1478-3975/abd0db apa: Lenne, P. F., Munro, E., Heemskerk, I., Warmflash, A., Bocanegra, L., Kishi, K., … Tlili, S. (2021). Roadmap for the multiscale coupling of biochemical and mechanical signals during development. Physical Biology. IOP Publishing. https://doi.org/10.1088/1478-3975/abd0db chicago: Lenne, Pierre François, Edwin Munro, Idse Heemskerk, Aryeh Warmflash, Laura Bocanegra, Kasumi Kishi, Anna Kicheva, et al. “Roadmap for the Multiscale Coupling of Biochemical and Mechanical Signals during Development.” Physical Biology. IOP Publishing, 2021. https://doi.org/10.1088/1478-3975/abd0db. ieee: P. F. Lenne et al., “Roadmap for the multiscale coupling of biochemical and mechanical signals during development,” Physical biology, vol. 18, no. 4. IOP Publishing, 2021. ista: Lenne PF, Munro E, Heemskerk I, Warmflash A, Bocanegra L, Kishi K, Kicheva A, Long Y, Fruleux A, Boudaoud A, Saunders TE, Caldarelli P, Michaut A, Gros J, Maroudas-Sacks Y, Keren K, Hannezo EB, Gartner ZJ, Stormo B, Gladfelter A, Rodrigues A, Shyer A, Minc N, Maître JL, Di Talia S, Khamaisi B, Sprinzak D, Tlili S. 2021. Roadmap for the multiscale coupling of biochemical and mechanical signals during development. Physical biology. 18(4), 041501. mla: Lenne, Pierre François, et al. “Roadmap for the Multiscale Coupling of Biochemical and Mechanical Signals during Development.” Physical Biology, vol. 18, no. 4, 041501, IOP Publishing, 2021, doi:10.1088/1478-3975/abd0db. short: P.F. Lenne, E. Munro, I. Heemskerk, A. Warmflash, L. Bocanegra, K. Kishi, A. Kicheva, Y. Long, A. Fruleux, A. Boudaoud, T.E. Saunders, P. Caldarelli, A. Michaut, J. Gros, Y. Maroudas-Sacks, K. Keren, E.B. Hannezo, Z.J. Gartner, B. Stormo, A. Gladfelter, A. Rodrigues, A. Shyer, N. Minc, J.L. Maître, S. Di Talia, B. Khamaisi, D. Sprinzak, S. Tlili, Physical Biology 18 (2021). date_created: 2021-04-25T22:01:29Z date_published: 2021-04-14T00:00:00Z date_updated: 2023-08-08T13:15:46Z day: '14' ddc: - '570' department: - _id: AnKi - _id: EdHa doi: 10.1088/1478-3975/abd0db ec_funded: 1 external_id: isi: - '000640396400001' pmid: - '33276350' file: - access_level: open_access checksum: 4f52082549d3561c4c15d4d8d84ca5d8 content_type: application/pdf creator: cziletti date_created: 2021-04-27T08:38:35Z date_updated: 2021-04-27T08:38:35Z file_id: '9355' file_name: 2021_PhysBio_Lenne.pdf file_size: 6296324 relation: main_file success: 1 file_date_updated: 2021-04-27T08:38:35Z has_accepted_license: '1' intvolume: ' 18' isi: 1 issue: '4' language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 project: - _id: B6FC0238-B512-11E9-945C-1524E6697425 call_identifier: H2020 grant_number: '680037' name: Coordination of Patterning And Growth In the Spinal Cord - _id: 268294B6-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P31639 name: Active mechano-chemical description of the cell cytoskeleton - _id: 05943252-7A3F-11EA-A408-12923DDC885E call_identifier: H2020 grant_number: '851288' name: Design Principles of Branching Morphogenesis publication: Physical biology publication_identifier: eissn: - 1478-3975 publication_status: published publisher: IOP Publishing quality_controlled: '1' related_material: record: - id: '13081' relation: dissertation_contains status: public scopus_import: '1' status: public title: Roadmap for the multiscale coupling of biochemical and mechanical signals during development tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 18 year: '2021' ...