Integrins are involved in a vast number of cell behaviors due to their roles in adhesion and signaling. The regulation of integrin expression is of particular interest as a mechanism to drive developmental events and for the role of altered integrin expression profiles in cancer. Dynamic regulation of the expression of integrin receptors is required for the migration of the distal tip cell (DTC) during gonadogenesis in Caenorhabditis elegans. integrin
ina-1 is required for DTC motility, yet is up-regulated by an unknown mechanism. Analysis of the promoter for integrin
ina-1 identified two E-box sequences that are required for
ina-1 expression in the DTC. Knockdown of transcription factor
hlh-2, an established E-box binding partner and ortholog of E/Daughterless, prevented expression of a transcriptional fusion of the
ina-1 promoter to RFP and blocked DTC migration. Similarly, knockdown of
hlh-2 also prevented expression of a translational fusion of the genomic
ina-1 gene to GFP while blocking DTC migration. Knockdown of HLH-2 binding partner MIG-24 also reduced
ina-1 expression and DTC migration. Overall, these results show that the transcription factor
hlh-2 is required for up-regulation of
ina-1 at the onset of DTC migration.