Cell and Developmental Biology University of Michigan

Research in my lab is focused on the cellular and molecular biology of brain development, injury and regeneration. Currently two lines of research are being explored. The first is injury-induced neuronal regeneration in teleost fish; the second is ocular morphogenesis in mammals.

A hallmark of the human brain is that neural injuries are permanent; destroyed neurons are never replaced. In contrast, in the retina of the teleost fish, neuronal death stimulates regenerative neurogenesis and replacement of the damaged tissue. We are interested in the cellular and molecular events that underlie this phenomenon. We use a variety of techniques, including microscopy, immunocytochemistry, organ culture and molecular biology, in an attempt to identify the molecules and genes that are critical in the response of mature neurons to injury and the stimulation of neurogenesis.

As an example of the second line of research in my lab, we are currently investigating early eye and retinal development in a line of transgenic mice that have an insertional mutation that results in ocular colobomas. This research is a collaboration with the lab of William Richardson, Ph.D. at University College London, where the mice were originally identified. We are presently characterizing the embryonic and early postnatal development of the eye and retina in these animals as well as attempting to clone the gene that accounts for the phenotype.

Publications

Representative Publications

• Raymond, P.A., Hitchcock, P.F. (2000) How the neural retina regenerates. Results & Problems in Cell Differentiation. 31:197-218.
• Otteson, D.C., D'Costa, A.R., Hitchcock, P.F. (2001) Putative stem cells and the lineage of rod photoreceptors in the mature retina of the goldfish. Developmental Biology. 232:62-76.
• Otteson, D.C., Cirenza, P.F. Hitchcock, P.F. (2002) Persistent neurogenesis in the teleost retina: evidence for regulation by the growth-hormone/insulin-like growth factor-I axis. Mech. Dev. 117:137-149.
• Otteson, D.C., Hitchcock, P.F. (2003) Stem cells in the teleost retina: persistent neurogenesis and injury-induced regeneration. Vision Res. 43:927-936.
• Hitchcock, P.F., M. Ochocinska, A. Sieh, D. C. Otteson (2004) Persistent and injury-induced neurogenesis in the vertebrate retina. Prog. Retinal Res. 23:183-194.
• Hitchcock, P.F. and L. Kakuk-Atkins (2004) The bHLH transcription factor neuroD is expressed in the rod lineage of the teleost retina. J. Comp. Neurol., 477(1):108-17.
• Ayayagari, R., M.N.A. Mandal, A. J. Karoukis, L. Chen., N.C. McLaren, M. Lichter, D.T. Wong, P. F. Hitchcock, R.C.. Caruso, S.E. Moroi, I.H. Maumenee, P.A. Sieving. (2005) Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. Invest. Ophthal. Visual Sci., 46:3363-3371.
• Chang B, Dacey MS, Hawes NL, Hitchcock PF, Milam AH, Atmaca-Sonmez P, Nusinowitz S, Heckenlively JR. (2006) Cone photoreceptor function loss-3, a novel mouse model of achromatopsia due to a mutation in Gnat2. Invest Ophthalmol Vis Sci.47:5017-21.
• Mandal MN, Vasireddy V, Reddy GB, Wang X, Moroi SE, Pattnaik BR, Hughes BA, Heckenlively JR, Hitchcock PF, Jablonski MM, Ayyagari R.(2006) CTRP5 is a membrane-associated and secretory protein in the RPE and ciliary body and the S163R mutation of CTRP5 impairs its secretion. Invest Ophthalmol Vis Sci. 2006 47:5505-13.
• Ochocinska, M and P.F. Hitchcock. (2007) Cellular expression of the bHLH transcription factor, neuroD, in the retina of the embryonic and larval zebrafish. J. Comp. Neurol. 501:1-12