Abstract
Little is known about the molecular mechanisms and intrinsic factors that are responsible for the emergence of neuronal subtype identity. Several transcription factors that are expressed mainly in precursors of the ventral telencephalon have been shown to control neuronal specification, but it has been unclear whether subtype identity is also specified in these precursors, or if this happens in postmitotic neurons, and whether it involves the same or different factors. SOX1, an HMG box transcription factor, is expressed widely in neural precursors along with the two other SOXB1 subfamily members, SOX2 and SOX3, and all three have been implicated in neurogenesis. SOX1 is also uniquely expressed at a high level in the majority of telencephalic neurons that constitute the ventral striatum (VS). These neurons are missing in Sox1-null mutant mice. In the present study, we have addressed the requirement for SOX1 at a cellular level, revealing both the nature and timing of the defect. By generating a novel Sox1-null allele expressing β-galactosidase, we found that the VS precursors and their early neuronal differentiation are unaffected in the absence of SOX1, but the prospective neurons fail to migrate to their appropriate position. Furthermore, the migration of non-Sox1-expressing VS neurons (such as those expressing Pax6) was also affected in the absence of SOX1, suggesting that Sox1-expressing neurons play a role in structuring the area of the VS. To test whether SOX1 is required in postmitotic cells for the emergence of VS neuronal identity, we generated mice in which Sox1 expression was directed to all ventral telencephalic precursors, but to only a very few VS neurons. These mice again lacked most of the VS, indicating that SOX1 expression in precursors is not sufficient for VS development. Conversely, the few neurons in which Sox1 expression was maintained were able to migrate to the VS. In conclusion, Sox1 expression in precursors is not sufficient for VS neuronal identity and migration, but this is accomplished in postmitotic cells, which require the continued presence of SOX1. Our data also suggest that other SOXB1 members showing expression in specific neuronal populations are likely to play continuous roles from the establishment of precursors to their final differentiation.
Highlights
The telencephalon is subdivided into dorsal and ventral territories, which give rise to the cerebral cortex and the underlying basal ganglia, respectively
We have previously shown that SOX1 is essential for the terminal differentiation of lens fibers and the activation of ccrystallins [37], and for the development of ventral striatum (VS) neurons, the lack of which is associated with epilepsy [34]
Mice homozygous for Sox1bgeo are null for SOX1 and exhibit the same phenotype as the previously described mice, which carry a deletion of the SOX1 coding region (Sox1M1)
Summary
The telencephalon is subdivided into dorsal (pallial) and ventral (subpallial) territories, which give rise to the cerebral cortex and the underlying basal ganglia, respectively. Several distinct types of neurons originate in the ganglionic eminences, and some migrate as far as the olfactory bulb, hippocampus, and neocortex [1,2,3], while others contribute more locally. The majority of neurons of the lateral ganglionic eminence (LGE) form the dorsal and ventral striatum (VS). The VS includes the caudate, putamen, nucleus accumbens, and olfactory tubercle (OT), which control various aspects of motor, cognitive, and emotional functions [4,5]. Little is known about the molecular mechanisms that control the emergence of various groups of neurons with distinct identities in this region
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