Apoptosis in metanephric development.

Abstract

Abstract. During metanephric development, non-polarized mesenchymal cells are induced to form the epithelial structures of the nephron following interaction with extracellular matrix proteins and factors produced by the inducing tissue, ureteric bud. This induction can occur in a transfilter organ culture system where it can also be produced by heterologous cells such as the embryonic spinal cord. We found that when embryonic mesenchyme was induced in vitro and in vivo, many of the cells surrounding the new epithelium showed morphological evidence of programmed cell death (apoptosis) such as condensed nuclei, fragmented cytoplasm, and cell shrinking. A biochemical correlate of apoptosis is the transcriptional activation of a calcium-sensitive endonuclease. Indeed, DNA isolated from uninduced mesenchyme showed progressive degradation, a process that was prevented by treatment with actinomycin-D or cycloheximide and by buffering intracellular calcium. These results demonstrate that the metanephric mesenchyme is programmed for apoptosis.Incubation of mesenchyme with a heterologous inducer, embryonic spinal cord prevented this DNA degradation. To investigate the mechanism by which inducers prevented apoptosis we tested the effects of protein kinase C modulators on this process. Phorbol esters mimicked the effects of the inducer and staurosporine, an inhibitor of this protein kinase, prevented the effect of the inducer. EGF also prevented DNA degradation but did not lead to differentiation. These results demonstrate that conversion of mesenchyme to epithelia requires at least two steps, rescue of the mesenchyme from apoptosis and induction of differentiation.

Apoptosis in the cortex of the developing mouse kidney

“…Nevertheless, these results remain compatible with the suggestion of Koseki et al (1992) that local cell death in the stroma of the cortex may facilitate nephron morphogenesis.…”

Effects of Low Protein Intake on the Development of the Remaining Kidney in Subtotally Nephrectomized Immature Rats: Apoptosis and Epidermal Growth Factor

“…Therefore, the present study suggests that EGF may play an important role in reduction of TUNEL positive cells in the Lp rats. This is supported by several lines of evidence as follows: superfluous apoptosis occurs in bcl-2 deficient mice and results in an increased number of apoptotic cells in the kidney [21]; EGF is one of the survival factors that protect the cells from apoptosis [19]; EGF prevents the degradation of DNA in rat renal mesenchyme [11]. Consequently, the present study reveals that low protein intake in subtotal nephrectomy in immature rats prevents renal failure and it is related to a recovery of EGF expression.…”

Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects inBMP7 deficient embryos

“…A reduction in the rate of growth or extent of branching of the ureter would, over time, decrease the amount of metanephric mesenchyme in the vicinity of a tip of the branched ureter. Because metanephric mesenchyme undergoes apoptosis in the absence of induction (Koseki et al, 1992), this could account for progressive cessation of inductive interactions in BMP7 deficient kidneys (Dudley et al, 1995;Luo et al, 1995).…”

“…The majority of cell death is observed in cells adjacent to developing nephrons and in cells of the proximal part of the developing tubule (Koseki et al, 1992;Coles et al, 1993). Apoptotic cells are not observed in the metanephric mesenchyme of the normal kidney.…”