The distribution and role of Ten-m3 in the developing retinogeniculate and retinocollicular projections in the wallaby Macropus eugenii
Creators: name: Carr, Owen Peter
Publisher: name: The Australian National University
Year: 2013
Subjects: subject: QL737.M35 C37 2013
subject: Macropus eugenii GeneticsAustralia
subject: Macropus eugenii Sense organs
subject: Retina Anatomy
subject: Visual pathways

description: The projections from the retina to the visual centres of the brain, such as the dorsal lateral geniculate nucleus and superior colliculus, are organised into retinotopic maps. These maps represent the spatial identity of visual information in the pattern of axonal connections formed and are particularly important for binocular vision, which requires the retinotopically accurate matching of projections from both eyes. Retinotopic guidance cues provide a chemical basis for forming retinotopic maps. Such cues are exemplified by the Eph/ephrin family, though an integrative effect of multiple different cues seems to underlie the formation of retinotopic maps. Ten-m3, a member of the Teneurin family of glycoproteins, is a homophilic transmembrane protein that is prominently expressed in the visual system during development and is a candidate retinotopic guidance cue that has been reported previously to be involved in the formation of binocular maps. The tammar wallaby (Macropus eugenii) is a representative model marsupial macropod, whose protracted ex utero development and sophisticated visual system are highly advantageous traits for the investigation of the developing visual system. These traits allow for the spatially and temporally restricted manipulation of Ten-m3 to investigate its function during development of the visual system in a manner that is not feasible in placental species. This study firstly determined the pattern of expression of mRNA for Ten-m3 in the developing visual system of the wallaby as a basis for subsequently investigating its function. Quantitative polymerase chain reaction found that during development the mRNA for Ten-m3 is higher in ventral than dorsal retina and higher in the retinotopically corresponding medial compared to lateral superior colliculus. It is also expressed at higher levels early in development, compared to later. In situ hybridisation demonstrated retinotopically corresponding gradients of expression of Ten-m3 in these tissues at all developmental ages examined. Specifically, an increasing dorsoventral gradient in retinal ganglion cells was matched to an increasing ventrolateral to dorsomedial gradient in the dorsal lateral geniculate nucleus, and an increasing lateromedial gradient in the superior colliculus. These gradients fit with the expectations of a retinotopic guidance cue and suggest that Ten-m3 could, through homophilic interactions, exert an axon-attractant effect and contribute to the mapping of the dorsoventral retinal axis in these visual centres. Overexpression of Ten-m3 by in vivo electroporation in nasal subregions of the retina and tracing projections from the whole eye showed no detectable effects on contralateral retinal projections. Rather, ipsilateral projections to the future binocular (medial and rostral) colliculus were increased, fitting with the proposal that Ten-m3 mediates mapping by axon-attractant homophilic interactions. Depending on the nasal subregion of the retina targeted, the ipsilateral retinogeniculate projection extended ventrolaterally, beyond the normal dorsal binocular zone of the nucleus. The changes mediated by increased levels of Ten-m3 could be due to either recruiting more ganglion cells to project ipsilaterally, or by specifically changing the behaviour of existing ipsilaterally projecting ganglion cells. The findings described in this thesis complement studies in the Ten-m3 knockout mouse and suggest that the role of Ten-m3 in contributing to the binocular retinal map is conserved between marsupial and placental mammalian species.