The Roles of the Robo2 and Robo3 Receptors in the Development of Cortical Interneurons

This thesis focuses on the putative roles of the Robo2 and Robo3 receptors in regulating the development of cortical interneurons and Cajal-Retzius cells in the embryonic mouse forebrain. A detailed analysis of the expression patterns of the Robo3 receptor is elucidated for the first time. Further comparison of all three Robos with interneuron markers confirms that different populations of cortical interneurons express these receptors during development. The putative roles of the Robo2 and Robo3 receptors in specifying the total number and distribution of cortical interneurons during development is investigated in vivo, using transgenic mice deficient in these receptors. This analysis shows that removal of the Robo2 or Robo3 receptors alone does not result in significant changes in the total numbers or positioning of interneurons within the cortex, suggesting that these receptors are not involved in the ventral-dorsal tangential migration of interneurons from their origins within the ganglionic eminences to the cortex. However, both Robo2 and Robo3 receptors significantly regulate the morphology of migrating interneurons during development. Preliminary analysis in triple Robo mutant mice points to a complex interplay between these receptors, and highlights the importance of understanding the functional relationship between these. In addition, a population of pioneering CajalRetzius cells express Robo receptors during preplate stages of development. Analysis in single Robo mutant animals suggests that Robo2 has a role in determining the total numbers of (reelin immunopositive) Cajal-Retzius cells within the hippocampal cortex.