The U-shaped C. elegans hermaphrodite gonad arms are formed by migration of two distal tip cells (DTCs). The gene
ppn-1 was identified in our genome-wide RNAi screen for genes required for DTC migration.
ppn-1 encodes the extracellular matrix (ECM) protein papilin that is required throughout nematode development; null mutants are arrested at embryonic or early larval stages. RNAi depletion of PPN-1 during larval development blocks gnoadogenesis by preventing initiation of DTC migration along the ventral basement membrane. This phenotype is very similar to loss of
gon-1 which encodes an ADAMTS matrix metalloprotease. PPN-1 contains a papilin protein interaction cassette that is also found in GON-1. Using a
ppn-1p::GFP transcriptional fusion line, GFP expression was observed in DTCs, neurons, body wall muscles, and vulva muscles. GFP was first observed in DTC precursor cells in the gonad primordium in developing embryos and the expression was continuous throughout DTC migration but down-regulated in DTCs of adult hermaphrodites. RNAi depletion of the HLH-2 transcription factor gives a similar ventral migration defect as loss of
ppn-1 or
gon-1 expression and almost completely eliminates GFP levels in DTCs of
ppn-1p::GFP nematodes. These results suggest that a developmental program controls initiation of DTC migration through expression of two essential ECM proteins. It has been shown that the
gon-1(0) gonad defect is rescued by mutation of
fbl-1, encoding the ECM protein fibulin-1. In contrast, neither a
fbl-1 mutant or FBL-1 depletion by RNAi was able to rescue the migration or sterility defects induced by loss of PPN-1. Thus, while
ppn-1 and
gon-1 expression patterns are overlapping and gonad phenotypes are similar, these ECM proteins appear to have distinct activities in initiation of DTC migration.