Sculpting the embryo as we wish!
Sculpting the embryo as we wish!
Our aim is to understand the cellular and molecular mechanisms underlying the morphogenetic processes that shape the embryo. How do cells behave collectively within the same population and communicate with different cell populations in three dimensions?
We use the gastrulating zebrafish embryo as a model system. With this system we can combine high resolution live-imaging analyses with sophisticated genetic manipulations to try and understand the following questions:
1. How do mesenchymal cells or epithelial cells keep themselves from behaving randomly?
2. How do normal cells detect transformed cells in a simple epithelium and eliminate them from the epithelium at the initiation of carcinogenesis?
3. How do epithelial cells co-ordinate their shape changes and propagate tension across the tissue?
Anton KA, Kajita M, Narumi R, Fujita Y, Tada M.
Src-transformed cells hijack mitosis to extrude from the epithelium.
Nat Commun. 2018 Nov 8;9(1):4695. doi: 10.1038/s41467-018-07163-4.
Smutny M, Akos Z, Grigolon S, Shamipour S, Ruprecht V, Capek D, Behrndt M, Papusheva E, Tada M, Hof B, Vicsek T, Salbreux G and Heisenberg CP (2017) Friction forces position the neural anlage. Nat. Cell Biol. (in press).
Saitoh S, Maruyama T, Yako Y, Kajita M, Fujioka Y, Ohba Y, Kasai N, Sugama N, Kon S, Ishikawa S, Hayashi T, Yamazaki T, Tada M and Fujita Y (2017) Rab5-regulated endocytosis plays a crucial role in apical extrusion of transformed cells. PNAS (in press).
Hernandez-Bejarano M, Gestri G, Spawls L, Nieto-Lopez F, Picker A, Tada M, Brand M, Bovolenta P, Wilson SW and Cavodeassi F (2015) Opposing Shh and Fgf signals initiate nasotemporal patterning of the zebrafish retina. Development 142, 3933-3942.
Kajita M, Sugimura K, Ohoka A, Burden J, Suganuma H, Ikegawa M, Shimada T, Kitamura T, Shindoh M, Ishikawa S, Yamamoto S, Saitoh S, Yako Y, Takahashi R, Okajima T, Kikuta, Maijima Y, Ishii M., Tada M and Fujita Y (2014) Filamin acts as a key regulator in epithelial defence against transformed cells. Nat. Commun. 5, 4428 doi: 10.1038/ncomms5428.
Hori A, Ikebe C, Tada M and Toda T (2014) Msd1/SSX2IP-dependent microtubule anchorage ensures spindle orientation and primary cilia formation. EMBO Rep.15, 175-185.
Lepage SE, Tada M and Bruce AE (2014) Zebrafish Dynamin is required for maintenance of enveloping layer integrity and the progression of epiboly. Dev. Biol. 385, 52-66.
Tada M and Heisenberg CP (2012) Convergent extension: using collective cell migration and cell intercalation to shape embryos. Development, 139, 3897-3904.
Tada M and Kai M (2012) Planar cell polarity in co-ordinated and directed movements. Curr. Topic Dev. Biol. 101, 77-110.
Norman M, Anton Wisniewska K, Lawrenson K, Garcia-Miranda P, Tada M, Kajita M, Mano H, Ishikawa S, Ikegawa M, Shimada T and Fujita Y (2012) Loss of Scribble causes cell competition in mammalian cells. J. Cell Sci. 125, 59–66.
Carmona-Fontaine C, Theveneau E, Tzekou A, Tada M, Woods M, Page K, Parsons M, Lambris J and Mayor R (2011) Complement fragment C3a controls mutual cell attraction during collective cell migration. Dev. Cell 21, 1026-1037.
Mapp OM, Walsh GS, Moens C, Tada M and Prince VR (2011) Zebrafish prickle1b mediates facial branchio-motor neuron migration via a farnesylation-dependent nuclear activity. Development 138, 2121-2132.
Trichas G, Joyce B, Crompton LA, Wilkins V, Clements M, Tada M, Rodriguez TA and Srinivas S (2011) Nodal dependent differential localisation of disheveled-2 demarcates regions of differing cell behaviour in the visceral endoderm. PLoS Biol. Feb;9(2):e1001019.
Kajita M, Hogan C, Harris A, Dupre-Crochet S, Itasaki N, Kawakami K, Charras G, Tada M and Fujita Y (2010) Interaction with surrounding normal epithelial cells influences signalling pathways and behaviour of Src-transformed cells. J. Cell Sci., 123, 171-180.
Carreira-Barbosa F, Kajita M, Morel V, Wada H, Okamoto H, Martinez Arias A, Fujita Y, Wilson SW and Tada M (2009) Flamingo regulates epiboly and convergence/extension movements through cell cohesive and signaling functions during zebrafish gastrulation. Development 136, 383-392.
Kai M, Heisenberg CP and Tada M (2008) Sphingosine-1-phosphate receptors regulate individual cell behaviours underlying the directed migration of prechordal plate progenitor cells during zebrafish gastrulation. Development 135, 3043-3051.
Beales PL, Bland E, Tobin JL, Bacchelli C, Hill J, Rix S, Pearson C, Kai M, Hartley J, Johnson C, Irving M, Elcioglu N, Tuysuz B, Winey M, Tada M and Scambler PJ (2007) The homologue of the intraflagellar transport protein, IFT80, is mutated in Jeune Asphyxiating Thoracic Dystrophy (JATD). Nat. Genet. 39, 727-729.
Tawk M, Araya C, Lyons DA, Reugels AM, Girdler GC, Bayley PR, Hyde DR, Tada M and Clarke J.DW (2007) A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis. Nature 446, 797-800.
Caneparo L, Huang YL, Staudt N, Tada M, Ahrendt R, Kazanskaya O, Niehrs C and Houart C (2007) Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/bcatenin and Wnt/PCP activities, through interaction with Dally-like homologue Knypek. Genes Dev. 21, 465-480.
Witzel S, Zimyanin V, Carreira-Barbosa F, Tada M * and Heisenberg CP* (2006) Wnt11 controls cell-cell contact persistence by local accumulation of Frizzled-7 at the plasma membrane. J. Cell Biol. 175, 791-802. *Corresponding authors.
Ross AJ, May-Simera H, Eichers ER, Kai M, Hill J, Jagger D, Leitch CC, Chapple JP, Munro PM. Fisher S, Phillips HM, Leroux MR, Henderson DJ, Murdoch JN, Copp AJ, Lupski JR, Tada M, Katsanis N, Forge A and Beales PL (2005) Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nat. Genet. 37, 1135-1140.
Carreira-Barbosa F, Concha ML, Takeuchi M, Ueno N, Wilson SW and Tada M(2003) Prickle1 regulates cell movements during gastrulation and neuronal migration in zebrafish. Development 130, 4037-4046.
*Heisenberg CP, *Tada M, Rauch GJ, Saude L, Concha ML, Geisler RE, Stemple DL, Smith JC and Wilson SW (2000) Silberblick/Wnt11 activity mediates convergent extension movements during zebrafish gastrulation. Nature 405, 76-81. *These authors contributed equally.
Our work is generously supported by: