Talk:Renal System - Molecular
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Cite this page: Hill, M.A. (2019, July 15) Embryology Renal System - Molecular. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Renal_System_-_Molecular
Epithelial cell fate in the nephron tubule is mediated by the ETS transcription factors etv5a and etv4 during zebrafish kidney development
Dev Biol. 2016 Mar 15;411(2):231-45. doi: 10.1016/j.ydbio.2016.01.035. Epub 2016 Jan 29.
Marra AN1, Wingert RA2.
Kidney development requires the differentiation and organization of discrete nephron epithelial lineages, yet the genetic and molecular pathways involved in these events remain poorly understood. The embryonic zebrafish kidney, or pronephros, provides a simple and useful model to study nephrogenesis. The pronephros is primarily comprised of two types of epithelial cells: transportive and multiciliated cells (MCCs). Transportive cells occupy distinct tubule segments and are characterized by the expression of various solute transporters, while MCCs function in fluid propulsion and are dispersed in a "salt-and-pepper" fashion within the tubule. Epithelial cell identity is reliant on interplay between the Notch signaling pathway and retinoic acid (RA) signaling, where RA promotes MCC fate by inhibiting Notch activity in renal progenitors, while Notch acts downstream to trigger transportive cell formation and block adoption of an MCC identity. Previous research has shown that the transcription factor ets variant 5a (etv5a), and its closely related ETS family members, are required for ciliogenesis in other zebrafish tissues. Here, we mapped etv5a expression to renal progenitors that occupy domains where MCCs later emerge. Thus, we hypothesized that etv5a is required for normal development of MCCs in the nephron. etv5a loss of function caused a decline of MCC number as indicated by the reduced frequency of cells that expressed the MCC-specific markers outer dense fiber of sperm tails 3b (odf3b) and centrin 4 (cetn4), where rescue experiments partially restored MCC incidence. Interestingly, deficiency of ets variant 4 (etv4), a related gene that is broadly expressed in the posterior mesoderm during somitogenesis stages, also led to reduced MCC numbers, which were further reduced by dual etv5a/4 deficiency, suggesting that both of these ETS factors are essential for MCC formation and that they also might have redundant activities. In epistatic studies, exogenous RA treatment expanded the etv5a domain within the renal progenitor field and RA inhibition blocked etv5a in this populace, indicating that etv5a acts downstream of RA. Additionally, treatment with exogenous RA partially rescued the reduced MCC phenotype after loss of etv5a. Further, abrogation of Notch with the small molecule inhibitor DAPT increased the renal progenitor etv5a expression domain as well as MCC density in etv5a deficient embryos, suggesting Notch acts upstream to inhibit etv5a. In contrast, etv4 levels in renal progenitors were unaffected by changes in RA or Notch signaling levels, suggesting a possible non-cell autonomous role during pronephros formation. Taken together, these findings have revealed new insights about the genetic mechanisms of epithelial cell development during nephrogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. KEYWORDS: Epithelial cell fate; Kidney; Multiciliated cells; Nephrogenesis; Notch signaling; Pronephros; Retinoic acid; etv4; etv5a PMID 26827902
A self-avoidance mechanism in patterning of the urinary collecting duct tree
BMC Dev Biol. 2014 Sep 10;14:35. doi: 10.1186/s12861-014-0035-8.
Davies JA1, Hohenstein P2, Chang CH3, Berry R4.
BACKGROUND: Glandular organs require the development of a correctly patterned epithelial tree. These arise by iterative branching: early branches have a stereotyped anatomy, while subsequent branching is more flexible, branches spacing out to avoid entanglement. Previous studies have suggested different genetic programs are responsible for these two classes of branches. RESULTS: Here, working with the urinary collecting duct tree of mouse kidneys, we show that the transition from the initial, stereotyped, wide branching to narrower later branching is independent from previous branching events but depends instead on the proximity of other branch tips. A simple computer model suggests that a repelling molecule secreted by branches can in principle generate a well-spaced tree that switches automatically from wide initial branch angles to narrower subsequent ones, and that co-cultured trees would distort their normal shapes rather than colliding. We confirm this collision-avoidance experimentally using organ cultures, and identify BMP7 as the repelling molecule. CONCLUSIONS: We propose that self-avoidance, an intrinsically error-correcting mechanism, may be an important patterning mechanism in collecting duct branching, operating along with already-known mesenchyme-derived paracrine factors.
Cell and molecular biology of kidney development
Semin Nephrol. 2009 Jul;29(4):321-37. doi: 10.1016/j.semnephrol.2009.03.009.
Reidy KJ1, Rosenblum ND.
Abnormalities of kidney and urinary tract development are the most common cause of end-stage kidney failure in childhood in the United States. Over the past 20 years, the advent of mutant and transgenic mice and the manipulation of gene expression in other animal models has resulted in major advances in identification of the cellular and molecular mechanisms that direct kidney morphogenesis, providing insights into the pathophysiology of renal and urologic anomalies. This review focuses on the molecular mechanisms that define kidney progenitor cell populations, induce nephron formation within the metanephric mesenchyme, initiate and organize ureteric bud branching, and participate in terminal differentiation of the nephron. Highlighted are common signaling pathways that function at multiple stages during kidney development, including signaling via Wnts, bone morphogenic proteins, fibroblast growth factor, sonic hedgehog, RET/glial cell-derived neurotrophic factor, and notch pathways. Also emphasized are the roles of transcription factors Odd1, Eya1, Pax2, Lim1, and WT-1 in directing renal development. Areas requiring future investigation include the factors that modulate signaling pathways to provide temporal and site-specific effects. The evolution of our understanding of the cellular and molecular mechanisms of kidney development may provide methods for improved diagnosis of renal anomalies and, hopefully, targets for intervention for this common cause of childhood end-stage kidney disease. PMID 19615554
Growth Factors Receptors
Fgfr1, Fgfr2 Fibroblast Growth Factor Receptor 1, 2 early metanephric development UB, MM
Gfrα1 GDNF Family Receptor Alpha 1 outgrowth of cells from the WD towards the MM UB, MM
Notch 2 Neurogenic locus notch homolog protein 2 maturation of proximal end of the nephron MM
Ret Receptor tyrosine-protein kinase initial ureteric bud outgrowth from Wolfian duct, interacts with GDNF ureteric bud epithelial cells
BRN1 Brain-Specific Homeobox/POU Domain Protein 1 tubule formation S-shaped body
FoxC2 Forkhead Box C2 first signal in podocyte commtiment s-shaped body
LIM1 (LHX1) LIM homebox 1 initial stages of patterning in the renal vesicle PTA, c-shaped body
Osr1 Odd-Skipped Related Transcription Factor 1 giving rise to MM intermediate mesoderm, MM
Sall1 Spalt-Like Transcription Factor 1 ensures high level of GDNF production MM
Pax2 Paired box gene 2 Expression in the MM ensures high level of GDNF production UB epithelial cells and condensed MM
Wt1 Wilms tumor 1 ensures high level of GDNF production cap MM-high levels, stromal MM-low levels, glomerular progenitors
β-catenin cadherin-associated protein beta nephron formation in the early stage of kidney development several cell types
Eya1 Eyes absent homolog 1 very early kidney development MM
HoxA11, HoxC11, HoxD11 homeobox protein A11, C11, D11 early kidney development uninduced MM
Six1 Sine oculis-related homeobox 1 early kidney development uninduced MM
Six2 Sine oculis-related homeobox 2 maintain nephron progenitor cells subpopulation of cells in cap MM