Singh et al. (2006) used RNA interference to decrease the expression of the Drosophila FLCN homologue (DBHD), and showed that DBHD was required for male germline stem cell (GSC) maintenance in the fly testis. Subsequent investigation suggested that DBHD regulates GSC maintenance downstream of, or in parallel to, the JAK/STAT and Decapentaplegic (Dpp) signal-transduction pathways.
The JAK-STAT signalling cascade regulates stem cell renewal and differentiation. Additionally, Dpp is the Drosophila homologue of the vertebrate bone morphogenetic proteins (BMPs), which are members of the TGF-β superfamily – a signalling system that is crucial for regulating a variety of cellular functions (Ying et al., 2003).
Further studies by Singh & Hou (2009) showed that over-expression of JAK-STAT signalling results in the enlargement of the Malphigian tubules (the Drosphila equivalent of the kidneys), coupled with an increased number of proliferating cells, mitotically active cells and putative renal stem cells. Thus, aberrant JAK-STAT signalling could contribute to the renal cystic/carcinoma phenotype observed in BHD syndrome.
