Metanephric mesenchyme

WT1 is present in the metanephric mesenchyme before induction and is upregulated during induction. Blocking induction stops the production of WT1. WT1 is expressed at high levels during the condensation of the mesenchyme and its transition to epithelium. Its expression diminishes thereafter, except in the podocyte layer of Bowman s capsule. WT1 knockout mice do not develop kidneys. The metanephric mesenchyme from these mice cannot be induced by wild-type inducers. 

A number of small proteins, such as BMP-7, Wingless-Int (WNT) and fibroblast growth factor (FGF-2), are candidate molecules for metanephric mesenchyme induction. BMP-7 is produced in the right place, BMP-7 knockout leads to renal agenesis and antibodies to BMP-7 block nephrogenesis in vitro. However, it is produced by tissues that cannot induce nephrogenesis in a co-culture. This suggests that BMP-7 is necessary for most, but perhaps not the earliest, events in... 

The metanephric mesenchyme has an extremely high rate of proliferation. The metanephros doubles in size every 8 h during the first 5 days. In the prospective renal cortex, the expression of PCNA, a marker for S-phase, occurs in a majority of cells. The proliferation rate is slowed significantly in BMP-7 knockouts (described above) and BF-2 knockouts. BF-2 is a transcription factor in the medullary stroma. It is likely that it controls the synthesis of a soluble growth factor that stimulates mesenchyme proliferation, but the identity of that factor is unknown. 

Thus, the metanephric mesenchyme contains multipotent progenitors or embryonic renal stem cells with the ability to generate, in concert with the ureteric bud, many cell types in the mature kidney. While the ultimate goal is the identification of a single nephrogenic stem cell that... 

Fig. 15.1 (a) A simplified scheme of an embryonic renal progenitor unit consisting of metanephric mesenchymal stem cells and ureteric buds, which cross-talk via growth factors (GFs) and their receptors, molecules of the extracellular matrix (ECM) and specific integrins, proto-oncogenes and specific ligands and give rise to the differentiated cell types of the adult kidney (see text). 

Recent advances in the understanding of the molecular biology of rodent renal development have enabled the separate culture of the components of the developing rat kidney, namely the ureteric bud and the metanephric mesenchyme. Functionally recombining subcultures of each of... 

Almeida-Porada G, El Shabrawy D, Porada C, et al. Differentiative potential of human metanephric mesenchymal cells. Exp. Hematol. 2002 30 1454-1462. 

Defects in the ENS are significant in view of the association of RET with Hirshsprung s disease. The ENS derives from neural crest cells which express Ret when in the developing gut and both Gdnf and Gfr-al are expressed in the gut mesenchyme. Lack of kidneys in mutant mouse embryos is due to the failure of the ureteric bud (which expresses Ret) to develop from the Wolffian duct and expand into the metanephric blastema (which expresses Gdnf). This would normally initiate the formation of the metanephric (adult) kidney, but in the absence of ligand or receptor the blastemal cells eventually die. 

Plisov SY, Ivanov Sy Yoshino K, Dove LF, Plisova TM, Higinbotham KG, Karavanova I, Lerman M, Perantoni AO. Mesenchymal-epithelial transition in the developing metanephric kidney gene expression study by differential display. Genesis 2000 ... 

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