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SUMMARY:Extracellular matrix remodelling by lead chick cranial neural cres
 t cells is a major determinant of robust collective migration - William Ma
 rtinson (University of Oxford)
DTSTART:20230718T150500Z
DTEND:20230718T151000Z
UID:TALK201688@talks.cam.ac.uk
DESCRIPTION:Collective cell migration plays an essential role in vertebrat
 e development\, yet the extent to which dynamically changing microenvironm
 ents influence this phenomenon remains unclear. Observations of the distri
 bution of the extracellular matrix (ECM) component fibronectin during the 
 migration of loosely connected neural crest cells (NCCs) lead us to hypoth
 esize that NCC remodeling of an initially punctate ECM creates a scaffold 
 for trailing cells\, enabling them to form robust and coherent stream patt
 erns. We evaluate this idea in a theoretical setting by developing an indi
 vidual-based computational model that incorporates reciprocal interactions
  between NCCs and their ECM. ECM remodeling\, haptotaxis\, contact guidanc
 e\, and cell-cell repulsion are sufficient for cells to establish streams 
 in silico\, however\, additional mechanisms\, such as chemotaxis\, are req
 uired to consistently guide cells along the correct target corridor. Furth
 er model investigations imply that contact guidance and differential cell-
 cell repulsion between leader and follower cells are key contributors to r
 obust collective cell migration by preventing stream breakage. Global sens
 itivity analysis and simulated gain- and loss-of-function experiments sugg
 est that long-distance migration without jamming is most likely to occur w
 hen leading cells specialize in creating ECM fibers\, and trailing cells s
 pecialize in responding to environmental cues by upregulating mechanisms s
 uch as contact guidance.
LOCATION:Seminar Room 1\, Newton Institute
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