Talk:Renal System - Fetal
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Cite this page: Hill, M.A. (2021, September 28) Embryology Renal System - Fetal. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Renal_System_-_Fetal
Mechanism of alcohol-induced impairments in renal development: Could it be reduced retinoic acid?
Clin Exp Pharmacol Physiol. 2011 Aug 30. doi: 10.1111/j.1440-1681.2011.05597.x. [Epub ahead of print]
Gray SP, Cullen-McEwen LA, Bertram JF, Moritz KM. Source Department of Anatomy & Developmental Biology, Monash University, Clayton, VIC 3800, Australia School of Biomedical Sciences, University of Queensland, QLD 4072, Australia.
1. Prenatal alcohol exposure impairs kidney development resulting in a reduced nephron number. However, the mechanism through which alcohol acts to disrupt renal development is largely unknown. Retinoic acid is critically involved in kidney development and it has been proposed that a diminished concentration is a contributing factor to fetal alcohol syndrome. 2. In this study we proposed that the ethanol-induced inhibition of ureteric branching morphogenesis and glomerular development in the cultured rat kidney would be ameliorated by co-culture with exogenous retinoic acid, and that examining the expression profile of key genes involved in the development of the kidney would provide insights into potential molecular pathways involved. 3. Whole rat metanephroi cultured in the presence of exogenous retinoic acid without ethanol appeared larger and had significantly more ureteric branch points, tips and glomeruli than metanephroi cultured in control media. Those cultured in the presence of ethanol alone (0.2%) had 20% fewer ureteric branch points, tips and glomeruli, which was ameliorated by co-culture with retinoic acid. 4. Gene expression analysis identified changes in the expression levels of enzymes involved in the metabolism of alcohol, in conjunction with changes in key regulators of kidney development including cRET. 5. These results demonstrate that the teratogenic effects of alcohol in vitro on kidney development resulting in reduced ureteric branching morphogenesis and glomerular development can be ameliorated through co-culture with retinoic acid. These results provide the foundation for future research into the mechanism through which alcohol acts to disrupt kidney development.
Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.
Betaglycan is required for the establishment of nephron endowment in the mouse
PLoS One. 2011 Apr 18;6(4):e18723.
Walker KA, Sims-Lucas S, Caruana G, Cullen-McEwen L, Li J, Sarraj MA, Bertram JF, Stenvers KL. Source Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia. Kenneth.Walker@princehenrys.org
Betaglycan is an accessory receptor for the transforming growth factor-β (TGFβ) superfamily, many members of which play key roles in kidney development. The purpose of this study was to define the role of this co-receptor on fetal murine kidney development. Stereological examination of embryonic and adult betaglycan heterozygous kidneys revealed augmented nephron number relative to littermate controls. Fetal heterozygous kidneys exhibited accelerated ureteric branching, which correlated with augmented nephron development at embryonic day (e) 15.5. In contrast, betaglycan null kidneys exhibited renal hypoplasia from e13.5 and reduced nephron number at e15.5. Quantitative real-time PCR analysis of e11.5-e14.5 kidneys demonstrated that heterozygous kidneys exhibited a transient decrease in Bmp4 expression at e11.5 and a subsequent cascade of changes in the gene regulatory network that governs metanephric development, including significant increases in Pax2, Eya1, Gdnf, Ret, Wnt4, and Wt1 expression. Conversely, gene expression in null kidneys was normal until e13.5, when significant reductions were detected in the expression of Bmp4 as well as other key metanephric regulatory genes. Tgfb1 and Tgfb2 mRNA expression was down-regulated in both nulls and heterozygotes at e13.5 and e14.5. The opposing morphological and molecular phenotypes in betaglycan heterozygote and null mutants demonstrate that the levels of betaglycan must be tightly regulated for optimal kidney development.
Renin expression in large renal vessels during fetal development depends on functional beta1/beta2-adrenergic receptors
Am J Physiol Renal Physiol. 2011 Jul;301(1):F71-7. Epub 2011 Mar 9.
Neubauer B, Machura K, Schnermann J, Wagner C. Source Physiologisches Institut, Universität Regensburg, D-93040 Regensburg, Germany.
During nephrogenesis, renin expression shifts from large renal arteries toward smaller vessels in a defined spatiotemporal pattern, finally becoming restricted to the juxtaglomerular position. Chronic stimulation in adult kidneys leads to a recruitment of renin expression in the upstream vasculature. The mechanisms that control this characteristic switch-on and switch-off in the immature and adult kidney are not well-understood. Previous studies in mice with juxtaglomerular cell-specific deletion of the adenylyl cyclase-stimulatory G protein Gsα suggested that signaling along the cAMP pathway plays an essential role for renin expression during nephrogenesis and in the adult kidney. To identify the Gsα-dependent receptor that might be involved in activating this pathway, the present studies were performed to compare renin expression in wild types with that in mice with targeted deletions of β(1) and β(2)-adrenoceptors. The sympathetic nervous system is an important regulator of the renin system in the adult kidney so that activation of β-adrenenoceptors may also participate in the activation of renin expression along the developing arterial tree and in upstream vasculature in adulthood. Compared with wild-types, renin expression was found to be significantly lower at all developmental stages in the kidneys of β(1)/β(2) Adr(-/-) mice. Three-dimensional analysis showed reduced renin expression in all segments of the vascular tree in mutants and a virtual absence of renin expression in the large arcuate arteries. Adult mutant kidneys showed the typical upstream renin expression after chronic stimulation. Tyrosine hydroxylase staining in fetal and postnatal kidneys revealed that sympathetic innervation of renin-producing cells occurs early in fetal development. Our data indicate that genetic disruption of β-adrenergic receptors reduces basal renin expression along the developing preglomerular tree and in adult kidneys. Furthermore, β-adrenergic receptor input is critical for the expression of renin in large renal vessels during early fetal development.
Comment in Am J Physiol Renal Physiol. 2011 Jul;301(1):F70.