|Title:||The role of Ten-m3 in the development of the mouse thalamostriatal pathway|
|Publisher:||University of Sydney.|
Department of Physiology.
School of Medical Sciences.
|Abstract:||Thalamostriatal afferents originating from the parafascicular nucleus (PF) target the striatal matrix in a topographically organised and patchy distribution. The molecular mechanisms underlying the development of this pathway are unknown. We have identified Ten-m3, a transmembrane glycoprotein, as the first molecular candidate in the formation of this circuit. Ten-m3 is expressed in the striatal matrix and PF in topographically corresponding high-dorsal to low-ventral gradients. In the striatum, this is overlaid on a patchy expression pattern. In Ten-m3 knock-out mice, thalamic terminals remain confined to the matrix but show altered topography, and the patchy patterning of terminals is lost. Evidence suggests that changes may be region specific. These anatomical changes correlate with delayed motor-skill learning in Ten-m3 knock-outs. During development, temporal expression of Ten-m3 correlates with the first ingrowth of thalamostriatal branches, and Ten-m3-positive patches overlap with dense clusters of thalamic terminals. Complex differences are observed throughout development in Ten-m3 knock-outs. In addition to direct homophilic mechanisms, we propose that Ten-m3 may act indirectly by altering levels of Epha7. Together, these data suggest that Ten-m3 acts via multiple mechanisms to organise topography and instruct complex organisation of thalamic terminals within the striatal matrix for the development of normal motor learning strategies.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (Open Access)|
|TRAN Heidi - Final thesis1.pdf||4.2 MB||Adobe PDF|
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