The follistatin knockout mouse: insights into kidney morphogenesis
Follistatin is an important regulator of cell growth and differentiation and plays a central role in organogenesis. However, the role of follistatin in kidney development has not been explored in detail. The current study examined the histology of kidneys from newborn follistatin homozygous null mutant (knockout) mice, and also cultured kidneys from these mice in order to identify developmental abnormalities in ureteric branching morphogenesis and nephrogenesis. Newborn follistatin knockout mice demonstrated renal developmental dysgenesis including ureteric branching abnormalities in the papilla leading to hydronephrosis. Whole metanephroi from embryonic day 12.5 wildtype, heterozygote and homozygous null mice were cultured for 3 days and immunostained with antibodies directed against calbindin D-28K (to identify ureteric tree) and the Wilm’s tumour antigen (WT1; to identify glomerular podocyte). Preliminary qualitative studies have demonstrated comparable ureteric morphogenesis and glomerulogenesis in cultured wildtype and heterozygote kidneys, but reduced branching and glomerulogenesis in the knockout kidneys. These findings suggest that follistatin signalling regulates normal branching morphogenesis and glomerular development during kidney development. Whether the decrease in glomerular number is due to a direct or indirect action (via inhibition of branching) remains unknown. Further quantitative studies of cultured explants will be conducted to extend our understanding of the pathogenesis of kidney abnormalities in follistatin knockout mice.