HOXD3 regulates expression of JAGGED1, a ligand for Notch receptors.

We generated transgenic mouse embryos expressing the human HOXD3 homeobox gene in the central nervous system (CNS) utilizing the Wnt1 expression vector. Whole mount in situ hybridization analysis revealed that the transgenic embryos at 10.5 days post coitum (dpc) expressed the HOXD3 gene in dorsal aspects of the CNS from the diencephalon to the spinal cord. Histological observation of sections showed that, in the spinal cord of the transgenic embryos at 10.5 dpc, there were few neuronal progenitor cells stretching from a luminal to basal side. This implies that Notch signaling which is involved in determining the courses of differentiation in the progenitors was disturbed within the CNS of the transgenic embryos. To elucidate what effects HOXD3 has on Notch signaling, we examined gene expression of Notch receptors and ligands using human erythroleukemia HEL and K562 cells transfected with the HOXD3 gene. Consequently, HOXD3 promoted expression of JAGGED1, a ligand for Notch receptors, in both the transfectants, suggesting that the JAGGED1 gene is a downstream target of HOXD3.

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