Periodic Reporting for period 1 - VIVO_MECH_COLL_MIGRA (Biomechanical analysis of in vivo directional collective migration)
Reporting period: 2016-02-02 to 2018-02-01
Finally, this grant was a great experience– it provided me with multidisciplinary collaborations, a complete toolbox to address new scientific questions, and it gave me managerial and leadership skills that I will use to obtain funding and lead my own research group.
Milestone 1.1. Mechanical properties of the neural crest and its surrounding tissues were effectively measured.
Milestone 1.2. The role of mechanical cues in directional NC migration in vivo was determined.
Milestone 1.3. I partially determined the interplay between mechanical and biochemical cues during directional NC migration. In vivo expeiments pending.
Work package 2. Identified part the molecular mechanism by which the mechanical properties of the substrate are sensed and translated as signals into the NC and analysed the role of Nedd9 as a key component of this process.
Milestone 2.1. I tested the potential of Nedd9 as a force-transducer in the NC. Additionally I showed that the NC uses Integrin, Vinculin, and Talin as sensors.
Milestone 2.2. Further experiments are required to fully understand the mechanism mediating the transduction of signals from the focal adhesions into the nucleus of NC cells.
For images supporting this findings and a more detailed story, please read Tech PartB Report; Barriga et al., Nature (doi:10.1038/nature25742); or http://thenode.biologists.com/mechanical-cues-developmental-pacers-orchestrate-morphogenesis/research/
The results of this grant were disseminated as follow:
Results from work packages 1 and 2 are published in:
Barriga et al., 2018: “Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo” Nature doi:10.1038/nature25742.
Barriga and Mayor, 2018: “Adjustable viscoelasticity allows for efficient collective cell migration” Seminars in Cell and Dev Biol, in press.
Results from Milestone 1.3 and 2.3 are in preparation for submission. This action will be appropriately acknowledged in future publications.
Results from Milestones 1.1 1.2 and 2.1: Abercrombie Meeting, Oxford, 2017; EMBO network meeting 2017; Developmental-Biology Symposium, Chile, 2018; Tissue Self Organisation: Challenging the systems, EMBL, 2018; and 18th Meeting of the International Society for Developmental Biology, Singapore, 2017.
Unpublished results from milestones 1.3 and 2.2 will be presented as a poster in the “Mechanobiology of Polarised Cells Meeting, France 2018”.
Kotini &, Elias H. Barriga &... and Mayor. Gap Junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo. (201X). Nature Communications. & these authors contributed equally.
Alkobtawi, Ray, Elias H Barriga… and Mayor (2018). Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development. Dev Biol doi: 10.1016/j.ydbio.2018.02.020
Bahm, Elias H. Barriga… and Mayor (2017). PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration. Development doi:10.1242/dev.147926
Rabadán, et al… (2016). Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by Dact1/2. Development doi:10.1242/dev.134981
-Highlights, Press, and Social media:
Disseminated results have been highlighted in web resources, social media, and Press. Very importantly this research was recommended by the F1000. This ensure that my research can outreach and have an impact in the non-scientific community.
Xenbase, Xenopus web resources. http://www.xenbase.org/entry/doNewsRead.do?id=581
F1000 recommendation: https://f1000.com/prime/732661919
The Node: http://thenode.biologists.com/mechanical-cues-developmental-pacers-orchestrate-morphogenesis/research/
UCL news: http://www.ucl.ac.uk/news/news-articles/0218/140218-tissue-mechanics
PhysOrg News: https://phys.org/news/2018-02-tissue-mechanics-essential-cell-movement.html