DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

We are interested in the mechanisms that direct development of the central nervous system (CNS) of vertebrates. Through lineage studies, we found that CNS progenitors generally are multipotent, with some exhibiting this even in their last cell division. As lineage alone does not appear to direct choice of cell fate of CNS cells, other signals are involved. We have chosen to focus on the signals in the vertebrate retina, a relatively simple and well-characterized area of the CNS. In vitro culture systems that mimic retinal development have been developed that allow study of the mitotic cycle, which is most likely intimately involved with cell fate decisions, as well as commitment and differentiation of retinal cells. These culture systems are being used to identify relevant extrinsic cues. In parallel, we are looking for intrinsic regulators. A recent approach is to use microarrays examine gene expression in single retinal progenitor cells and differentiating retinal cells. As well, we are cataloguing gene expression in all types of mature retinal neurons to enable the generation of markers for these cells and electrophysiological analysis in collaboration with other laboratories.

Publications

• Jadhav AP, Mason HA, Cepko CL.Notch 1 inhibits photoreceptor production in the developing mammalian retina.Development 2006 Mar;133(5):913-23.
  16452096
• Corbo JC, Cepko CL.A hybrid photoreceptor expressing both rod and cone genes in a mouse model of enhanced S-cone syndrome.PLoS Genet 2005 Aug;1(2):e11.
  16110338
• Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, Weber G, Lee K, Fraioli RE, Cho SH, Yung R, Asch E, Ohno-Machado L, Wong WH, Cepko CL.Genomic analysis of mouse retinal development.PLoS Biol 2004 Sep;2(9):E247.
  15226823
• Roesch K, Jadhav AP, Trimarchi JM, Stadler MB, Roska B, Sun BB, Cepko CL.The transcriptome of retinal Muller glial cells.J Comp Neurol 2008 May 8;509(2):225-238.
  18465787
• Damiani D, Alexander JJ, O'Rourke JR, McManus M, Jadhav AP, Cepko CL, Hauswirth WW, Harfe BD, Strettoi E.Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina.J Neurosci 2008 May 7;28(19):4878-87.
  18463241
• Lagali PS, Balya D, Awatramani GB, Munch TA, Kim DS, Busskamp V, Cepko CL, Roska B.Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration.Nat Neurosci 2008 Apr 27.
  18432197
• Matsuda T, Cepko CL.Analysis of gene function in the retina.Methods Mol Biol 2008;423:259-78.
  18370205
• Punzo C, Cepko CL.Ultrasound-guided in utero injections allow studies of the development and function of the eye.Dev Dyn 2008 Apr;237(4):1034-42.
  18351670
• Trimarchi JM, Stadler MB, Cepko CL.Individual retinal progenitor cells display extensive heterogeneity of gene expression.PLoS ONE 2008;3(2):e1588.
  18270576
• Kim DS, Ross SE, Trimarchi JM, Aach J, Greenberg ME, Cepko CL.Identification of molecular markers of bipolar cells in the murine retina.J Comp Neurol 2008 Feb 7;507(5):1795-1810.
  18260140
• Morrow EM, Chen CM, Cepko CL.Temporal order of bipolar cell genesis in the neural retina.Neural Develop 2008;3:2.
  18215319
• Rompani SB, Cepko CL.Retinal progenitor cells can produce restricted subsets of horizontal cells.Proc Natl Acad Sci U S A 2008 Jan 8;105(1):192-7.
  18162542
• Hsiau TH, Diaconu C, Myers CA, Lee J, Cepko CL, Corbo JC.The cis-regulatory logic of the mammalian photoreceptor transcriptional network.PLoS ONE 2007;2(7):e643.
  17653270
• Corbo JC, Myers CA, Lawrence KA, Jadhav AP, Cepko CL.A typology of photoreceptor gene expression patterns in the mouse.Proc Natl Acad Sci U S A 2007 Jul 17;104(29):12069-74.
  17620597
• Chen B, Cepko CL.Requirement of histone deacetylase activity for the expression of critical photoreceptor genes.BMC Dev Biol 2007;7:78.
  17603891
• Viney TJ, Balint K, Hillier D, Siegert S, Boldogkoi Z, Enquist LW, Meister M, Cepko CL, Roska B.Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing.Curr Biol 2007 Jun 5;17(11):981-8.
  17524644
• Trimarchi JM, Stadler MB, Roska B, Billings N, Sun B, Bartch B, Cepko CL.Molecular heterogeneity of developing retinal ganglion and amacrine cells revealed through single cell gene expression profiling.J Comp Neurol 2007 Jun 20;502(6):1047-65.
  17444492
• Cho SH, Cepko CL.Wnt2b/{beta}-catenin-mediated canonical Wnt signaling determines the peripheral fates of the chick eye.Development 2006 Aug;133(16):3167-77.
  16854977
• Zhang J, Gray J, Wu L, Leone G, Rowan S, Cepko CL, Zhu X, Craft CM, Dyer MA.Rb regulates proliferation and rod photoreceptor development in the mouse retina.Nat Genet 2004 Apr;36(4):351-60.
  14991054