Connections between brain regions continue to be made during adolescence (Spear, 2010). Axonal guidance, important in this process, is decreased in the hippocampus: 14 of the 17 altered genes in this pathway have decreased expression, including Tuba4a, Plxd1, Plxb3, Shank2, Mmp9 and Sema3c (Table 2). Tubulins are necessary for axonal outgrowth. Tuba4a, when mutated, is associated with cortical malformations (Romaniello, Arrigoni, Bassi, & Borgatti, 2015). Plexin D1 interacts with semaphorin 3E and is important in vascular and neural development (Oh & Gu, 2013). Plexin-B3, found in dendrites, promotes inhibitory synapse formation in the hippocampus and suppresses excitatory synapse production (Laht et al., 2015). A decrease in Plexin-B3 may reverse this trend, allowing more excitatory synapses to form. The three genes increased in the axonal guidance pathway are Semaphorin 3c, Adamts1 and neuropilin 2 (Tables 2, 3). Adamts1 cleaves semaphorin 3C from the extracellular matrix so that it can act in axon guidance and promote cell migration, (Esselens et al., 2010). Neuropilin 2 is a receptor for semaphorin 3F (which is expressed in the hippocampus) and functions similarly to the plexins.
