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Morphogenetic cell movements during development
Early development is marked by many cells undergoing substantial reorganisation to create the form of the embryo. We are interested in the mechanisms that control and enact these movements. In the laboratory we are using time-lapse microscopy and custom-built software to trace and analyse the dynamics of morphogenesis in the zebrafish embryo. This allows us to visualise both where cells go and to ask questions about how these movements shape tissues.
In recent work, along with our collaborators Alexandre Kabla (Department of Engineering, Cambridge) and L. Mahadevan (Harvard), we have developed a theory to link cell behaviour to tissue morphogenesis (Blanchard et al 2009). Tissue tectonics is a framework with which to measure the rate of tissue deformation at a very fine spatial and temporal scale. Tissue morphogenesis is then subdivided into contributions caused by changes in cell shape and those caused by cell rearrangement, or intercalation. This approach is very powerful in allowing us to see variations in cell behaviour in time and space and to distinguish the bases of mutant phenotypes (Butler et al. 2009; Gorfinkiel et al. 2009). For the first time we have a definition and continuous measure for cell intercalation, a cellular mechanism central to many aspects of animal development.
We offer projects to look at all aspects of this process: the acquisition and analysis of high-resolution time-lapse movies; the development of probes to reveal how cells respond to developmental signals; investigation of the mechanisms of cell rearrangements during morphogenesis; the development of analytical methods to measure and compare morphogenetic mechanisms. We are particularly interested in the development of the central nervous system during gastrulation and neurulation.
Cellular morphogenesis of the vertebrate central nervous system
My laboratory is interested in the morphogenetic development of early gastrula and neurula stages (England et al. 2006). We use zebrafish as a developmental model. We collect 3D time-lapse movies of embryos developing then perform quantitative analyses of the patterns of movements and reorganisation of cells that give rise to the emerging form of the embryo. We can compare the development of mutant and experimental animals with the normal situation using these quantitative assays and thus begin to understand the relationship between proteins and cell behaviour.
Sources of funding:
BBSRC & EPSRC
Blanchard GB & Adams RJ (2011) Measuring the multi-scale integration of mechanical forces during morphogenesis. Current Opinion in Genes & Development, 21, 653-663. pdf
Blanchard GB, Murugesu S, Adams RJ, Martinez-Arias A & Gorfinkiel N (2010) Cytoskeletal dynamics and supra-cellular organization of cell shape fluctuations during dorsal closure. Development, 137, 2743-2752. pdf
Kabla AJ, Blanchard GB, Adams RJ, & Mahadevan L (2010) Bridging cell and tissue behaviour in embryo development, In ‘Cell Mechanics: From Single Scale-Based Models to Multiscale Modelling’ Eds. Chauvière A, Preziosi L & Verdier C, Chapman & Hall.
Butler LC, Blanchard GB, Kabla AJ, Lawrence NJ, Welchman DP, Mahadevan L, Adams RJ & Sanson B (2009) Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germband extension. Nature Cell Biology, 11, 859-864. pdf
Gorfinkiel N, Blanchard GB, Adams RJ & Arias AM (2009) Mechanical control of global cell behaviour during Dorsal Closure in Drosophila. Development, 136, 1889-1898. pdf
Blanchard GB, Kabla AJ, Schultz NL, Butler LC,Sanson B, Gorfinkiel N, Mahadevan L & Adams RJ (2009) Tissue tectonics: morphogenetic strain rates, cell shape change and intercalation. Nature Methods, 6, 458-64. Pubmed pdf Supplementary
Meilhac et al. (2009) Active cell movements coupled to positional induction are involved in lineage segregation in the mouse blastocyst. Developmental Biology, 331, 210-21.
Svetic et al. (2007) Sdf1a patterns zebrafish melanophores and links the somite and melanophore pattern defects in choker mutants. Development, 134, 1011-22.
England SJ & Adams RJ (2007) Building a dynamic fate map. BioTechniques, 43 (1 Suppl), 20-4. pdf
Rembold et al. (2006) Individual cell migration serves as the driving force for optic vesicle evagination. Science, 313, 1130-4. pdf
Strauss et al. (2006) A default mechanism of spindle orientation based on cell shape is sufficient to generate cell fate diversity in polarised Xenopus blastomeres. Development, 133, 3883-93.
England SJ, Blanchard GB, Mahadevan L & Adams RJ (2006) A dynamic fate map of the forebrain shows how vertebrate eyes form and explains two causes of cyclopia. Development, 133, 4613-4617. pdf
Adams RJ & Kimmel CB (2003) Morphogenetic cellular flows during zebrafish gastrulation. In: "Gastrulation", ed: C. Stern.
Glickman NS, Kimmel CB, Jones MA and Adams RJ (2003) Shaping the zebrafish notochord. Development, 130, 873-887. pdf
Feldman B, Concha ML, Saude L, Parsons MJ, Adams RJ, Wilson SW and Stemple DL (2002) Current Biology, 12, 2129-2135.
Kane D and Adams RJ (2002) Zebrafish epiboly and involution. In "Pattern Formation in Zebrafish", Springer-Verlag. ed. Lila Solnica-Krezel.
Concha M and Adams RJ (1998) Oriented cell divisions and cellular morphogenesis in the zebrafish gastrula and neurula: a time-lapseanalysis. Development, 125, 983-994. pdf