Figure 9: Satb2- and Ctip2-dependent establishment of cortical connections.
From: Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation
(a) During early corticogenesis, cingulate neurons with high DCC expression form the pioneer axons for the CC. These axons respond to midline Netrin1 and are attracted towards the Netrin1 source. (b) Later, when Layer V cells start projecting medially, Satb2 represses Ctip2, thereby promoting Unc5C expression. These Unc5C axons are repelled by the Netrin1 source in the internal capsule and thus turn towards the midline. Corticofugally projecting neurons, however, express high Ctip2 and thus repress Unc5C. In addition, the lack of repression of DCC by Satb2, promotes high DCC levels in these neurons. Thus, these axons are attracted towards the internal capsule (c). Despite expressing high levels of Unc5C and low levels of DCC, upper layer neurons are not dependent on these molecules and instead either follow the deep layer callosal pioneer axons or are dependent on other axon guidance molecules. (d–f) Represent the scenario in the Satb2, Netrin1 or Unc5C mutants, respectively. In each of the mutants, the lack of an Unc5C-Netrin1 interaction causes a misrouting of deep layer callosal axons to subcortical targets.
