Tbr1 Regulates Differentiation of the Preplate and Layer 6

Abstract

During corticogenesis, early-born neurons of the preplate and layer 6 are important for guiding subsequent neuronal migrations and axonal projections. Tbr1 is a putative transcription factor that is highly expressed in glutamatergic early-born cortical neurons. In Tbr1-deficient mice, these early-born neurons had molecular and functional defects. Cajal-Retzius cells expressed decreased levels of Reelin, resulting in a reeler-like cortical migration disorder. Impaired subplate differentiation was associated with ectopic projection of thalamocortical fibers into the basal telencephalon. Layer 6 defects contributed to errors in the thalamocortical, corticothalamic, and callosal projections. These results show that Tbr1 is a common genetic determinant for the differentiation of early-born glutamatergic neocortical neurons and provide insights into the functions of these neurons as regulators of cortical development.

The determination of projection neuron identity in the developing cerebral cortex

“…Tbr1 is expressed in the preplate and layer 6 during early corticogenesis [40], and Tbr1-deficient mice show defects in preplate splitting and in the positioning of early-born neurons (similar to the migration defects observed in reeler mice) [41]. Indeed, in the absence of Tbr1, the expression of reelin by Cajal-Retzius cells in the marginal zone is reduced [41]. Tbr1 knockouts also exhibit a variety of axon projection defects, with corticothalamic projections growing only as far as the internal capsule, callosal projections mostly terminating in Probst bundle without crossing the midline, and thalamocortical projections reaching the internal capsule, but then turning away from the cortex and extending into the external capsule and amygdala.…”

“…Tbr1 is expressed in the preplate and layer 6 during early corticogenesis [40], and Tbr1-deficient mice show defects in preplate splitting and in the positioning of early-born neurons (similar to the migration defects observed in reeler mice) [41]. Indeed, in the absence of Tbr1, the expression of reelin by Cajal-Retzius cells in the marginal zone is reduced [41].…”

Disruption of Foxg1 expression by knock-in of Cre recombinase: Effects on the development of the mouse telencephalon

“…We therefore performed in situ hybridization (E16.5) or immunocytochemistry (P4), using markers that identified specific layers in the developing cortex, to examine potential laminar defects of Foxg1-Cre/+ mice during late corticogenesis and early postnatal development. Tbr1 is highly expressed in preplate and layer VI neurons soon after they differentiate (Bulfone et al, 1995, Hevner et al, 2001). There is a thickening of a zone of Tbr1 staining at E16.5 in Foxg1-Cre/+ mice ( Figure 7A, B), suggesting an abnormal representation of subplate and layer VI neurons in the cortex of heterozygous mice at this time.…”

Neural stem cells: mechanisms and modeling

“…Another well-studied transcription factor is Pax6, which is expressed in type 1 NSCs in the SGZ (Maekawa et al, 2005;Nacher et al, 2005;Hodge et al, 2008;Roybon et al, 2009) and in neuroblasts in the SVZ (Herold et al, 2011;Jones and Connor, 2011) and functions to promote the dopaminergic fate determination of NSCs (Kohwi et al, 2005;Brill et al, 2008;Spitere et al, 2008). A third example, Tbr1, is localized in the olfactory bulb and cortex and promotes the neuronal differentiation of NSCs in the SVZ (Hevner et al, 2001;Englund et al, 2005;Mé-ndez-Gómez et al, 2011). Although many other transcription factors (Hodge and Hevner, 2011) have been found to be present in adult NSCs or immature neurons, their exact functions in the maintenance and fate determination of adult NSCs remain elusive.…”