The Donoghue research group has long studied a group of surface-based intercellular signaling molecules that coordinate cerebral cortical development. Parcellated during primate and mouse corticogenesis (Sestan et al., 2001; Yun et al, 2003), Eph receptor/ephrin ligand interactions contribute to areal specification in the cerebral cortex (Miller et al., 2006), promote cortical proliferation (North et al., 2009) and guide sensory neuron axon targeting (North et al., 2010). Furthermore, collaborative work with biophysics laboratory at Georgetown demonstrated that EphA function alters synaptic connections (Clifford et al., 2011). Finally, a role for Eph signaling in segregating the developing thalamus was just completed (Lehigh et al., 2013). Most recently, we have revealed a role for one receptor in cortical neuronal maturation (Clifford et al., submitted). Ongoing projects in the lab, based upon co-expression of receptors and ligands during corticogenesis (Figure 1) reveals roles for Eph family members in cortical synaptic shape and function (Figure 2).
At the same time, Professor Donoghue has always had an interest in how cells in discrete parts of the nervous system are marked for specific fates (Donoghue and Sanes, 1994; Kolk et al., 2006). The lab has recently taken this interest in the direction of understanding the role of SoxC family of transcriptional activators and repressors. Initially, cell culture system was used to characterize SoxC function in neurons in vitro (Figure 3). We went on to examine roles of SoxC family members in proliferation and differentiation (Figure 4). Finally, differing roles of SoxC family members in the specification of cerebral cortical neurons have been examined (Figure 5). Our experiments reveal interesting differences in how related SoxC genes act during corticogenesis.