Analysis of dorsal midline CNS formation and fate using the Lmx genes

The roof plate is an important signaling center in the dorsal midline of the central nervous system (CNS). While the formation and function of the roof plate in the spinal cord has been examined in depth, the anterior midline of the CNS is not as well characterized. This thesis describes the analysis of the fate of the roof plate in the mouse from e8.5 into adulthood and the roles of Lmx1a and Lmx1b in the formation of dorsal midline signaling centers in the telencephalon. By generating a transgenic mouse line that expresses cre recombinase under the control of Lmx1a, I was able to follow the fate of roof plate cells from the initiation of transgene expression into adulthood. I found that roof plate cells are fated to become the most dorsal cells in the CNS and loss of roof plate signaling results in these cells adopting a more ventral fate. To remove dorsal midline signaling from the telencephalon, I generated embryos that lacked Lmx1a and Lmx1b function. I discovered that Lmx1a and Lmx1b function redundantly in the telencephalic neural epithelium and mesenchyme respectively to pattern the telencephalic midline. I present the first example of a role for dorsal telencephalic mesenchyme in patterning the telencephalic dorsal midline.