Head of Department
Where does the nervous system come from in the embryo? How does it grow to the right size and shape? How do stem cells turn into more committed neuronal progenitors and how do these cells know when to leave the cycle and differentiate into neural and glial progenitors? How do particular regions of the nervous system produce the right number of neurons and the right proportions of the different types of neurons? Once born, how do these precursors differentiate? How do they choose a particular cell type to become amongst a myriad of possible fates, and by what cellular mechanisms do these cells become properly polarised, branched, and integrated into the retinal circuitry? What mechanisms allow retinal ganglion cells to send out long axons that forge pathways to their targets in the brain, and recognise specific cells within these targets?
The visual systems of Xenopus and zebrafish are ideal for such questions because of their embryological, molecular and genetic accessibility to experimentation, combined with the possibility of in vivo time-lapse imaging. The retina is an excellent system to explore the issue of cellular proliferation and diversity. We are unravelling some of the lineage dependent and lineage independent events that are used to push or induce cells to transition from proliferating retinal stem cells to differentiated neurons and glia particular fates and testing a variety of hypotheses concerning the mechanisms of fate specification and histogenesis. We are using similar approaches to investigate the mechanisms involved in the initial morphogenesis of various retinal neuron types. We are also conducting a variety of experiments on how the growing axons gather and transduce the information that allows them to find their way to their targets, exploring the machinery and the dynamics of growth cones at a molecular level.
Pt IB NST Neurobiology; Pt IB MVST NAB/HNB; Pt II NST N1; Pt II NST Mod P6/L6; Graduate CDBC
Chow RW, Almeida AD, Randlett O, Norden C, Harris WA (2015), Inhibitory neuron migration and IPL formation in the developing zebrafish retina, Development, Aug 1;142(15):2665-77. PubMed PMID: 26116662
Almeida AD, Boije H, Chow RW, He J, Tham J, Suzuki SC, Harris WA (2014), Spectrum of Fates: a new approach to the study of the developing zebrafish retina, Development May;141(9):1971-80. PubMed PMID: 24718991
Randlett O, MacDonald RB, Yoshimatsu T, Almeida AD, Suzuki SC, Wong RO, Harris WA, (2013), Cellular requirements for building a retinal neuropil, Cell Rep. 3:282-90
He J, Zhang G, Almeida AD, Cayouette M, Simons BD, Harris WA, (2012), How variable clones build an invariant retina, Neuron, 75:786-98 PubMed PMID:22958820
Agathocleous M, Love NK, Randlett O, Harris JJ, Liu J, Murray AJ, Harris WA, (2012), Metabolic differentiation in the embryonic retina, Nat Cell Biol, 14:859-64
Randlett O, Poggi L, Zolessi FR, Harris WA, (2011), The oriented emergence of axons from retinal ganglion cells is directed by laminin contact in vivo, Neuron, 70:266-8
Norden C, Young S, Link BA, Harris WA, (2009), Actomyosin is the main driver of interkinetic nuclear migration in the retina, Cell, Sep 18;138(6):1195-208. PubMed PMID:19766571
Agathocleous M, Harris WA (2009), From progenitors to differentiated cells in the vertebrate retina, Annu Rev Cell Dev Biol. 25:45-69. PubMed PMID:19575661
Poggi L, Vitorino M, Masai I, Harris WA (2005), Influences on neural lineage and mode of division in the zebrafish retina in vivo, J Cell Biol, Dec 19;171(6):991-9. PubMed PMID:16365165
Zuber ME, Gestri G, Viczian AS, Barsacchi G, Harris WA, (2003), Specification of the vertebrate eye by a network of eye field transcription factors, Development, Nov;130(21):5155-67. PubMed PMID:12944429
Ohnuma S, Philpott A, Wang K, Holt CE, Harris WA, (1999), p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina, Cell, Nov24;99(5):499-510. PubMed PMID:10589678
Zuber ME, Perron M, Philpott A, Bang A, Harris WA, (1999), Giant eyes in Xenopus laevis by overexpression of XOptx2, Cell, Aug 6;98(3):341-52. PubMed PMID:10458609