mig-32 encodes a RING-domain protein identified in a yeast two hybrid screen seeking proteins that interact with UNC-3, the C. elegans ortholog of a family of variant mammalian HLH transcription factors.
mig-32 is expressed in most or all nuclei of embryos and larvae, and concentrates in some nucleoli.
mig-32 mutants have defects in axon guidance and in the migration of specific neurons. Defects include incomplete migration of the HSNs and failure of the HSNs to extend their axons to the vulva and nerve ring, anterior localization of the Ray1 neurons in the male tail, and commissural axon outgrowth of the DD and VD neurons on the wrong side. Weak defects in the position of the ALM and AVM neurons are present. Distal tip cell migration is normal, suggesting that
mig-32 is not generally required for cell migration. We are examining additional neurons and cells in
mig-32 mutants to define the relationship of
mig-32 to other genes that affect migration and axon pathfinding.
MIG-32 is the single C. elegans protein similar to the Polycomb group (PcG) family of transcriptional repressors that includes mammalian Bmi-1. Bmi-1 is a well-characterized member of the PRC1 complex, which represses transcription of target genes classically including Hox genes. A MIG-32::GAL4DBD fusion represses transcription with an efficiency similar to mouse Bmi-1 in transfected HEK293 cells, suggesting that MIG-32 can assemble a repression complex through conserved interactions with mammalian components. However, using several assays, we do not observe defects in Hox gene function or expression in
mig-32 mutants. These data suggest that MIG-32 may be a component of a repressor complex that regulates targets distinct from the mammalian PRC1 complex, and that it regulates neuronal migration and axon pathfinding through Hox-independent mechanisms.