This description of a model system for cell differentiation and organogenesis is written by one of the foremost researchers in the area. The main emphasis is on the mammalian kidney, but the book also deals with the development of the transien excretory organs. It includes discussions of induction, proliferation, early cytodifferentiation and morphogenesis and organogenesis. This authoritative account will be valuable to developmental biologists and also to scientists working in paediatric nephrology. As it gives the background of normal development and of control systems, it will also be of use to nephrologists working on abnormalities in the urinary tract.

The mammalian permanent kidney consists of three cell lineages of different origin: the epithelial cells of the ureter bud, the mesenchymal cells of the nephric blastema and the endothelial cells of the capillaries. Organogenesis is governed by a cascade of morphogenetic interactions between these cell populations, a reciprocal epithelial-mesenchymal interaction between the branching ureter and the metanephric mesenchyme, homotypic interactions between cells of the tubular anlagen, stimulation of angiogenesis by the differentiating blastema and a mesenchymal--endothelial interaction guiding the migration of the capillary endothelial cells. While the biology of these interactive events is well known, as described in this overview, the molecular mechanisms are less well mapped out.

We report that activin profoundly alters epithelial branching morphogenesis of embryonic mouse salivary gland, pancreas and kidney rudiments in culture, indicating that it may play a role as a morphogen during mammalian organogenesis. In developing pancreas and salivary gland rudiments, activin causes severe disruption of normal lobulation patterns of the epithelium whereas follistatin, an activin-binding protein, counteracts the effect of activin. In the kidney, activin delays branching of the ureter bud and reduces the number of secondary branches. TGF-beta induces a pattern of aberrant branching in the ureter bud derived epithelium distinct from that seen for activin. Reverse-transcriptase polymerase chain reaction, Northern hybridization and in situ hybridization analyses indicate that these developing tissues express the mRNA transcripts for activin subunits, follistatin or activin receptors. Our results are suggestive of a potential role for the activin-follistatin system as an intrinsic regulator of epithelial branching morphogenesis during mammalian organogenesis.

The glycoprotein laminin is found exclusively in the basement membranes of adult tissues, not in the mesenchymal stroma. We studied the appearance and distribution of laminin during the early formation of kidney tubules in mouse embryos and in an in vitro transfilter model system. In immunofluorescence using affinity-purified antibodies, the distribution of laminin showed a clear correlation, both spatially and temporally, to the early stages of tubule formation. In vivo, laminin was first detected in a punctate pattern in areas where the pretubular aggregates form; later, it became confined to the basement membranes of the tubules. In experiments in vitro, the nephrogenic mesenchyme was found to form tubules after 12-24 hr of transfilter contact with the inductor. The first laminin spots were found after 12 hr of culture, 24 hr before overt morphogenesis. As the mesenchymal cells began to aggregate and elongate (at 36 hr), laminin was detected in those cells destined to become epithelial, and at 48 hr it was not found in cells remaining in the stroma. In more mature tubules (at 72 hr), laminin was seen as a sharp band in the basement membranes.

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