title: The Acquisition of Target Dependence by Developing Rat Retinal Ganglion Cells
abstract: Similar to neurons in the peripheral nervous system, immature CNS-derived RGCs become dependent on target-derived neurotrophic support as their axons reach termination sites in the brain. To study the factors that influence this developmental transition we took advantage of the fact that rat RGCs are born, and target innervation occurs, over a protracted period of time. Early-born RGCs have axons in the SC by birth (P0), whereas axons from late-born RGCs do not innervate the SC until P4-P5. Birth dating RGCs using EdU allowed us to identify RGCs (1) with axons still growing toward targets, (2) transitioning to target dependence, and (3) entirely dependent on target-derived support. Using laser-capture microdissection we isolated ∼34,000 EdU(+) RGCs and analyzed transcript expression by custom qPCR array. Statistical analyses revealed a difference in gene expression profiles in actively growing RGCs compared with target-dependent RGCs, as well as in transitional versus target-dependent RGCs. Prior to innervation RGCs expressed high levels of BDNF and CNTFR α but lower levels of neurexin 1 mRNA. Analysis also revealed greater expression of transcripts for signaling molecules such as MAPK, Akt, CREB, and STAT. In a supporting in vitro study, purified birth-dated P1 RGCs were cultured for 24-48 h with or without BDNF; lack of BDNF resulted in significant loss of early-born but not late-born RGCs. In summary, we identified several important changes in RGC signaling that may form the basis for the switch from target independence to dependence.
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia.
authors.forename: Colette
authors.initials: C
authors.lastname: Moses
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia.
authors.forename: Lachlan P G
authors.initials: LP
authors.lastname: Wheeler
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia.
authors.forename: Chrisna J
authors.initials: CJ
authors.lastname: LeVaillant
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Kramer
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia.
authors.forename: Marisa
authors.initials: M
authors.lastname: Ryan
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia.
authors.forename: Greg S
authors.initials: GS
authors.lastname: Cozens
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia ; Department of Neuroscience, Karolinska Institutet , 17177 Stockholm, Sweden.
authors.forename: Anil
authors.initials: A
authors.lastname: Sharma
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pollett
authors.affiliation: School of Animal Biology, The University of Western Australia , Perth, Western Australia 6009, Australia ; Western Australian Neuroscience Research Institute , Nedlands, Western Australia 6009, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodger
authors.affiliation: School of Anatomy, Physiology, and Human Biology, The University of Western Australia , Perth, Western Australia 6009, Australia ; Western Australian Neuroscience Research Institute , Nedlands, Western Australia 6009, Australia.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Harvey
keywords: BDNF; neurotrophic factors; programmed cell death; retinal ganglion cells; target dependence