Fig. 6. PDGF roles in mammalian organogenesis. In several early developmental contexts, epithelial PDGF drives proliferation of undifferentiated mesenchyme expressing PDGFR. However, during organ maturation, PDGF signals direct several other cellular functions. (See text for more details.) (A) Cell migration and angiogenesis. In the developing kidney, PDGFB/PDGFRß signaling is essential for the migration of Pdgfrb-expressing endothelial/mesangial cell precursors (blue) from (a) the cleft of the S-shaped nephron into (b,c) the glomerular space. These cells give rise to the glomerular capillary bed (red) and its mesangial cells (pericyte-like cells that coat glomerular capillaries; c). (d) In Pdgfb- and Pdgfrb-null embryos, few Pdgfrb-expressing precursors migrate to the nephron cleft, and these cells fail to enter the glomerular space; capillary beds fail to form in these embryos and capillary aneurysms are observed in the glomerular space. The embryonic testis vasculature develops through the formation of the coelomic vessel (a', b') and the branching of this vessel between testis cords (c'). Endothelial cells (blue) migrate from the mesonephros into the testis, where they contribute to the coelomic vessel and its branches (red). PDGFR is required for both endothelial cell migration and branching of the coelomic vessel. In both the kidney and testis, PDGF signals may directly induce angiogenic branching of the primitive vasculature, although this has not been clearly shown in vivo. (B) Cellular differentiation and/or function. PDGF signals are essential for the differentiation and/or function of interstitial cell types in the developing testis. PDGFR is required for the differentiation of both fetal and adult Leydig cells. The ligand(s) required for fetal Leydig cell development are not yet known, but PDGFA is required for the development of adult Leydig cells, which replace fetal Leydig cells during postnatal testis maturation. There is evidence from in vitro studies that PDGF signals may induce perimyoid cell (PMC) differentiation and/or function. These cells originate in the interstitium and differentiate into contractile, smooth muscle-like cells that associate tightly with testis cords. Together, PMCs and Sertoli cells produce the basement membrane around cords. The source(s) of PDGFs that direct interstitial cell differentiation/function is not clear, although PDGFs are secreted from the coelomic vessel, the mesonephros and testis cords. (C) Epithelial folding. Pdgfra-expressing mesenchymal cells cluster at sites of future epithelial folding during lung, skin and intestine morphogenesis. Although the Pdgfra-expressing cells are essential for these morphogenetic processes, their roles and the role(s) of PDGF signaling in folding morphogenesis are not yet known. Late in embryogenesis, Pdgfra-positive mesenchymal cells (blue) in the lung migrate to sites of alveolar septation (a), a postnatal process in which the air sac epithelium invaginates and is lined with specialized matrix. Septation does not occur in the absence of the Pdgfra-positive cells, whose development requires PDGFA during embryogenesis. During intestine maturation, Pdgfra-positive mesenchymal cells (blue) cluster at sites of future villus formation (b). The intestinal epithelium subsequently folds into the lumen of the intestine and Pdgfra-positive cells migrate from the clusters to line the forming villus. Pdgfra expression is maintained in these cells during villus maturation, and, in PDGFA-null mice, villus structure and epithelial differentiation are abnormal.