TrkC-T1, the Non-Catalytic Isoform of TrkC, Governs Neocortical Progenitor Fate Specification by Inhibition of MAP Kinase Signaling.

Neocortical projection neurons are generated by neural progenitor cells (NPCs) within the ventricular and subventricular zone. While early NPCs can give rise to both deep and upper layer neurons, late progenitors are restricted to upper layer neurogenesis. The molecular mechanisms controlling the differentiation potential of early versus late NPCs are unknown.

Bcl11a (Ctip1) Controls Migration of Cortical Projection Neurons through Regulation of Sema3c.

During neocortical development, neurons undergo polarization, oriented migration, and layer-type-specific differentiation. The transcriptional programs underlying these processes are not completely understood. Here, we show that the transcription factor Bcl11a regulates polarity and migration of upper layer neurons.

Sip1 downstream Effector ninein controls neocortical axonal growth, ipsilateral branching, and microtubule growth and stability.

Sip1 is an important transcription factor that regulates several aspects of CNS development. Mutations in the human SIP1 gene have been implicated in Mowat-Wilson syndrome (MWS), characterized by severe mental retardation and agenesis of the corpus callosum. In this study we have shown that Sip1 is essential for the formation of intracortical, intercortical, and cortico-subcortical connections in the murine forebrain.

miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6.

miR-128, a brain-enriched microRNA, has been implicated in the control of neurogenesis and synaptogenesis but its potential roles in intervening processes have not been addressed. We show that post-transcriptional mechanisms restrict miR-128 accumulation to post-mitotic neurons during mouse corticogenesis and in adult stem cell niches. Whereas premature miR-128 expression in progenitors for upper layer neurons leads to impaired neuronal migration and inappropriate branching, sponge-mediated inhibition results in overmigration.

Ntf3 acts downstream of Sip1 in cortical postmitotic neurons to control progenitor cell fate through feedback signaling.

Cortical progenitors undergo progressive fate restriction, thereby sequentially producing the different layers of the neocortex. However, how these progenitors precisely change their fate remains highly debatable. We have previously shown the existence of cortical feedback mechanisms wherein postmitotic neurons signal back to the progenitors and promote a switch from neurogenesis to gliogenesis.

Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation.

The pyramidal neurons of the mammalian neocortex form two major types of long-range connections-corticocortical and cortico-subcortical. The transcription factors Satb2 and Ctip2 are critical regulators of neuronal cell fate that control interhemispheric versus corticofugal connections respectively. Here, we investigate the axon guidance molecules downstream of Satb2 and Ctip2 that establish these connections.