The goal of this research is to characterize the defects in the thalamus and the neocortex in Gbx-2 mutant mice. Gbx-2 is a homeodomain containing transcription factor expressed in the developing vertebrate nervous system. A null mutation in the Gbx-2 gene in the mouse was made by Dr. Gail Martin's laboratory and they have characterized abnormal cerebellar development. preliminary evidence from Dr. Rubenstein's laboratory suggests that the thalamus and he subsequent production of thalamocortical afferents is also defective in the Gbx-2 mutant mouse.
The first aim of the proposal is to describe the abnormalities in the thalamus of the Gbx-2 mice in terms of histological characterization and expression of various markers, known to be expressed at various stages of thalamus development. Markers are chosen based on questions of regional specification, proliferation and differentiation state, nuclei formation, and development of specific neuronal cell types.
This aim i s straight forward, must be executed carefully to make any conclusion, and potentially may reveal downstream effects of Gbx-2 function.
The second aim i s also descriptive and uses a straight forward DiI tracing approach to more fully characterize the preliminary observation of abnormal thalamocortical and corticofugal axonal projections in the Gbx-2 mutant brains. The first two aims are straight forward and are essential to understand the defect in the Gbx-2 mutant brains so that future studies can be better defined.
The third aim i s more hypothesis driven and asks the question whether neocortical development is affected in the absence of thalamocortical innervation. This question can be asked in the Gbx-2 mutant mice since Gbx-2 is not expressed in the neocortex (a fact I would be careful to verity so that conclusions can be made from these experiments) and thalamocortical axons do not reach the cortex. Birthdating and lamina-specific gene expression will be used to determine if the layers in the neocortex have developed normally or not and thus test the role of thalamocortical projections on neocortex layer formation.
