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SoxB1 sub-family of transcriptional regulators are expressed in progenitor (NP) cells throughout the neuroaxis and are generally downregulated during neuronal differentiation. Gain- and loss-of-function studies indicate that  Sox1 ,  Sox2  and  Sox3  are key regulators of NP differentiation and that their roles in CNS development are largely redundant. Nevertheless, mutation of each SoxB1 individually results in a different array of CNS defects, raising the possibility that SoxB1 proteins have subtly different functions in NP cells. To explore the mechanism of SOXB1 functional redundancy, and to identify genes that are most sensitive to loss of the  Sox3  gene, we performed genome wide expression profiling of  Sox3  null NP cells. Nineteen genes with abnormal expression were identified, including the homeobox gene  Dbx1 . Analysis of  Sox3  null embryos revealed that  Dbx1  was significantly reduced in the neural tube and developing brain and that SOX3 bound directly to conserved elements associated with this gene in cultured NP cells and  in vivo . These data define  Dbx1  as a direct SOX3 target gene whose expression, intriguingly, is not fully rescued by other SOXB1 transcription factors, suggesting that there are inherent differences in SOXB1 protein activity.

Dbx1 Is a Direct Target of SOX3 in the Spinal Cord