Although it has long been appreciated that
retinoids play an essential role in kidney organogenesis, it has only recently been recognized that even mild fetal
vitamin A deficiency syndromes can result in a reduction in nephron number. Recent studies have also begun to define the cellular and molecular events associated with
retinoid actions in the fetal kidney and have demonstrated the essential function of
retinoids in branching growth of the ureteric bud. Importantly, characterization of the renal developmental effects of RAR alpha/beta 2 double homozygous mice combined with metanephric organ culture studies have together shown that one essential function of
retinoid action in the developing kidney is the maintenance of c-ret expression in the
tips of the ureteric bud. However, many other potential
retinoid target genes including
midkine, sonic hedgehog, Hox d-11,
matrix metalloproteinases, and tissue inhibitors of
metalloproteinases appear to play important roles in renal development and might be important downstream mediators of
retinoid effects in the developing kidney. It can, therefore, be anticipated that important new insights into fetal kidney development will be forthcoming in the near future, as the essential target genes affected by
retinoid signal transduction are progressively elucidated.