Identification and functional characterization of two patterning genes, Zic4 and Ten_m3, in topographic map formation of the visual pathway

A central feature of visual pathway development is its organization into retinotopic maps. The developmental process by which these maps form involves a transition from early patterning cues to arrays of axonal guidance factors allowing the relative order of retinotopic axons to be preserved. Mechanisms linking patterning molecules of early development to topographic wiring and subsequent functional responses are not well understood. In this thesis, I performed a microarray screen comparing gene expression in early visual and auditory regions of the thalamus in order to identify early patterning candidates with a potential role in visual pathway differentiation. Among the candidates enriched in the visual thalamus, the transcription factor, Zic4, was found to be expressed in gradients of the developing retina, lateral geniculate nucleus (LGN) and primary visual cortex (V 1). Mice lacking Zic4 exhibited a deficit in eye-specific patterning to the thalamus that was complementary to the phenotype seen in mice lacking Tenm3, a type II homophilic transmembrane receptor and transcriptional regulator. Using intrinsic signal optical imaging techniques, I characterized the functional properties of primary visual cortical retinotopic maps in Zic4 and Ten_m3 null mice and identified complementary changes in the ipsilateral representation of V1, as well as evidence for eye-specific mismatch in the cortical binocular zone. Additionally, complementary positional shifts in VI were found in these mutants identifying a bidirectional modulation of mapping mechanisms in the visual pathway.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Horng, Sam H

Advisor dc:contributor.advisor

• Mriganka Sur.

• Brain and Cognitive Sciences.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/58371

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/58371