Branching morphogenesis and kidney disease

Shah, Mita M.; Sampogna, Rosemary V.; Sakurai, Hiroyuki; Bush, Kevin T.; Nigám, Sanjay K.

doi:10.1242/dev.01089

Cited by 155 publications

(150 citation statements)

References 144 publications

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“…The suboptimal nephron endowment caused by defects in branching morphogenesis may affect filtration function. 40 Podocyte-specific excision of Vangl2 led to a temporary glomerular developmental delay, and no tubular defects were detected, making it unlikely that it would have affected branching morphogenesis and thus, contributed to the observed enhanced response to the injury. However, throughout life, mice with loss of Vangl2 in podocytes displayed a modest but significant reduction in podocyte number per glomerulus.…”

Section: At 1 Year Of Age Vangl2mentioning

confidence: 95%

Deficiency of the Planar Cell Polarity Protein Vangl2 in Podocytes Affects Glomerular Morphogenesis and Increases Susceptibility to Injury

Rocque

Babayeva

et al. 2015

Journal of the American Society of Nephrology

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The planar cell polarity (PCP) signaling pathway is crucial for tissue morphogenesis. Van Gogh-like protein 2 (Vangl2) is central in the PCP pathway; in mice, Vangl2 loss is embryonically lethal because of neural tube defects, and mutations in Vangl2 are associated with human neural tube defects. In the kidney, PCP signaling may be important for tubular morphogenesis and organization of glomerular epithelial cells (podocytes) along the glomerular basement membrane. Podocyte cell protrusions (foot processes) are critical for glomerular permselectivity; loss of foot process architecture results in proteinuria and FSGS. Previously, we showed a profound effect of PCP signaling on podocyte shape, actin rearrangement, cell motility, and nephrin endocytosis. To test our hypothesis that the PCP pathway is involved in glomerular development and function and circumvent lethality of the ubiquitous Vangl2 mutation in the Looptail mouse, we generated a mouse model with a podocyte-specific ablation of the Vangl2 gene. We report here that podocyte-specific deletion of Vangl2 leads to glomerular maturation defects in fetal kidneys. In adult mice, we detected significantly smaller glomeruli, but it did not affect glomerular permselectivity in aging animals. However, in the context of glomerular injury induced by injection of antiglomerular basement membrane antibody, deletion of Vangl2 resulted in exacerbation of injury and accelerated progression to chronic segmental and global glomerular sclerosis. Our results indicate that Vangl2 function in podocytes is important for glomerular development and protects against glomerular injury in adult animals. 26: 576-586, 201526: 576-586, . doi: 10.1681 Renal glomerular visceral epithelial cells (podocytes) are highly polarized cells with complex threedimensional architecture characterized by the presence of unique actin-based projections (foot processes [FPs]). 1 The FPs from neighboring podocytes form intercellular bridges, slit diaphragms, that are the only points of contact between adjacent cells and the base for the permselective filtration barrier, allowing small solutes to pass into the urinary space while retaining large proteins in the blood. 1 Slit diaphragm protein complexes are connected with the podocyte cytoskeleton by various adaptor proteins and serve as a signaling nexus to relay information from the FP surface to control podocyte structure. 2 The characteristic shape of podocytes is directly related to glomerular filtration. Mutations in proteins that link slit diaphragms and the cytoskeleton (e.g., a-actinin-4 and CD2-associated protein) 3,4 or regulators of actin polymerization and organization (e.g., Inverted Formin-2, Myosin 1e, Rho GDP-Dissociation Inhibitor 1, and Cdc42) 5-9 give rise to glomerular dysfunction, such as proteinuria, J Am Soc Nephrol

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Section: At 1 Year Of Age Vangl2mentioning

confidence: 95%

Deficiency of the Planar Cell Polarity Protein Vangl2 in Podocytes Affects Glomerular Morphogenesis and Increases Susceptibility to Injury

Rocque

Babayeva

et al. 2015

Journal of the American Society of Nephrology

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“…The evidence for the functions of many of these factors in kidney development has been recently reviewed. (13)(14)(15) Here, we focus on one factor shown to have a particularly critical role in this process, the TGF-b family member glial cell-line-derived neurotrophic factor (GDNF).…”

Section: Introductionmentioning

confidence: 99%

GDNF/Ret signaling and the development of the kidney

2006

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SummarySignaling by GDNF through the Ret receptor is required for normal growth of the ureteric bud during kidney development. However, the precise role of GDNF/Ret signaling in renal branching morphogenesis and the specific responses of ureteric bud cells to GDNF remain unclear. Recent studies have provided new insight into these issues. The localized expression of GDNF by the metanephric mesenchyme, together with several types of negative regulation, is important to elicit and correctly position the initial budding event from the Wolffian duct. GDNF also promotes the continued branching of the ureteric bud. However, it does not provide the positional information required to specify the pattern of ureteric bud growth and branching, as its site of synthesis can be drastically altered with minimal effects on kidney development. Cells that lack Ret are unable to contribute to the tip of the ureteric bud, apparently because GDNF-driven proliferation is required for the formation and growth of this specialized epithelial domain.

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“…Indeed, branching morphogenesis is a fundamental developmental process involved in formation of a variety of organs, from fly trachea and air sacs, to mammalian lungs, kidneys, vasculature, pancreas, as well as many exocrine glands, including mammary and salivary glands [1]. As a result, a deeper understanding of branching morphogenesis is not only crucial to our understanding of how these organs develop, but to understanding the molecular etiology of many human diseases, such as polycystic kidney disease, kidney and lung agenesis, and many malignancies including breast and prostate cancer [2,3].…”

Section: Introductionmentioning

confidence: 99%

Comparative Mechanisms of Branching Morphogenesis in Diverse Systems

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Werb

2006

J Mammary Gland Biol Neoplasia

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Much progress has been made in recent years toward understanding mechanisms controlling branching morphogenesis, a fundamental aspect of development in a variety of invertebrate and vertebrate organs. To gain a deeper understanding of how branching morphogenesis occurs in the mammary gland, we compare and contrast the cellular and molecular events underlying this process in both invertebrate and vertebrate organs. Thus, in this review, we focus on the common themes that have emerged from such comparative analyses and discuss how they are implemented via a battery of signaling pathways to ensure proper branching morphogenesis in diverse systems.

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Branching morphogenesis and kidney disease

Cited by 155 publications

References 144 publications

Deficiency of the Planar Cell Polarity Protein Vangl2 in Podocytes Affects Glomerular Morphogenesis and Increases Susceptibility to Injury

Deficiency of the Planar Cell Polarity Protein Vangl2 in Podocytes Affects Glomerular Morphogenesis and Increases Susceptibility to Injury

GDNF/Ret signaling and the development of the kidney

Comparative Mechanisms of Branching Morphogenesis in Diverse Systems

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