PTEN modulates GDNF/RET mediated chemotaxis and branching morphogenesis in the developing kidney

Kim, Doyeob; Dressler, Gregory R.

doi:10.1016/j.ydbio.2007.04.051

Cited by 57 publications

(48 citation statements)

References 57 publications

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“…This hypothesis is supported by the observation that Pten is expressed in TuJ1+ cells behind the migration wavefront. These observations are consistent with known roles for Pten in the migration of neuronal precursors in the central nervous system van Diepen and Eickholt, 2008) and in other cells (Kim and Dressler, 2007;Leslie et al, 2007;Liliental et al, 2000;Sanchez et al, 2005;Tamura et al, 1998), supporting the hypothesis that Rarinduced changes in Pten are crucial for normal ENS development.Several novel aspects of this work should be emphasized. First, effects of RA on Pten are rarely reported.…”

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confidence: 88%

Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation

et al. 2010

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SUMMARYHirschsprung disease is a serious disorder of enteric nervous system (ENS) development caused by the failure of ENS precursor migration into the distal bowel. We now demonstrate that retinoic acid (RA) is crucial for GDNF-induced ENS precursor migration, cell polarization and lamellipodia formation, and that vitamin A depletion causes distal bowel aganglionosis in serum retinolbinding-protein-deficient (Rbp4 -/-) mice. Ret heterozygosity increases the incidence and severity of distal bowel aganglionosis induced by vitamin A deficiency in Rbp4 -/-animals. Furthermore, RA reduces phosphatase and tensin homolog (Pten) accumulation in migrating cells, whereas Pten overexpression slows ENS precursor migration. Collectively, these data support the hypothesis that vitamin A deficiency is a non-genetic risk factor that increases Hirschsprung disease penetrance and expressivity, suggesting that some cases of Hirschsprung disease might be preventable by optimizing maternal nutrition. MATERIALS AND METHODS Mice Rbp4-/- (Quadro et al., 2005) and Ret +/-mice (Enomoto et al., 2001) were bred >10 generations to C57BL/6. For timed breeding studies, the day of the vaginal plug was considered as embryonic day 0.5 (E0.5). Wild-type CF-1 mice were from Charles River. Mice were maintained on Purina PICO irradiated mouse diet 5058 until E7.5. Food was changed to synthetic chow (El Mel, St Charles, MO, USA) containing sufficient vitamin A (TestDiet 5755; 22.1 IU vitamin A/g) or to vitamin A deficient food (TestDiet 5822; <0.4 IU vitamin A/g) colored blue or yellow to avoid confusion. Mice were maintained on synthetic diets until analysis. Retinoid measurementsRA was quantified using an API-4000 (Applied Biosystems) LC/MS/MS with atmospheric pressure chemical ionization in positive ion mode. Retinol and retinyl esters were quantified by HPLC/UV (Kane et al., 2008a). Tissues were harvested under yellow light, immediately frozen in liquid N 2 and kept at -80°C until assay. Samples were homogenized on ice, extracted and analyzed as described (Kane et al., 2005;Kane et al., 2008b). Total protein was determined by Bradford (Bio-Rad). Slice cultureE12.5 CF-1 midgut sections (300-400 m length) from 400 m proximal to the cecum were cultured on fibronectin-coated (250 g/ml) dishes in Opti-MEM (Invitrogen), glutamine (2 mM), penicillin 100 IU/ml and streptomycin 100 g/ml. Immediately after plating, cells were treated with RA (10 -7 M, Sigma, St Louis, MO, USA) or BMS493 (10 -5 M, generously provided by Dr Chris Zusi at Bristol-Myers Squibb). GDNF (100 ng/ml) was added to cultures three hours later. Cultures were maintained for 16 hours before fixation [4% paraformaldehyde (PFA), 10 minutes, 25°C]. Boyden chamberTranswell supports (8.0 m pore size; 0.33 cm 2 area; Corning 3422; Fisher Scientific) were coated on both sides with 10% Matrigel (Fisher Scientific) in PBS (4°C, 18 hours) and rinsed with PBS. Neural crest medium [Dulbecco's modified Eagle medium (DMEM), 10% chick embryo extract, 1% N2 supplement, 2% B27 supplement, penicil...

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supporting

confidence: 88%

Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation

et al. 2010

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“…As far as we know, this type of process does not occur normally during development of other epithelial organs, e.g., kidney or lung. Even though tubular morphogenesis in different organs utilizes apparently distinct mechanisms, many of the same molecules such as PI3K/Akt and HNF1␤ have been implicated in formation of a variety of tubular structures (Coffinier et al, 2002;Tang et al, 2002;Liu et al, 2004;Lebrun et al, 2005;Kim and Dressler, 2007). This suggests that there may be common principles of tubulogenesis that underlie seemingly diverse mechanisms of tubulogenesis.…”

Section: Discussionmentioning

confidence: 99%

Liver Progenitor Cells Fold Up a Cell Monolayer into a Double-layered Structure during Tubular Morphogenesis

Tanimizu

Miyajima

Mostov

2009

MBoC

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Bile ducts are hepatic tubular structures that are lined by cholangiocytes, a type of liver epithelial cell. Cholangiocytes first form a single layer of cells, termed the ductal plate, surrounding the portal vein, which eventually remodels into the branching tubular network of bile ducts. The process of bile duct morphogenesis is not yet clear: a conventional model where cholangiocytes proliferate to duplicate a single layer of the ductal plate before lumen formation seems inconsistent with the observation that proliferation is dramatically reduced when hepatoblasts, liver progenitor cells, differentiate into cholangiocytes. Here, we developed a new culture system in which a liver progenitor cell line, HPPL, reorganizes from a monolayer to tubular structures in response to being overlaid with a gel containing type I collagen and Matrigel. We found that some of the HPPL in the monolayer depolarized and migrated to fold up the monolayer into a double-cell layer. These morphogenetic processes occurred without cell proliferation and required phosphatidylinositol 3-kinase and Akt activity. Later in morphogenesis, luminal space was generated between the two cell layers. This process, in particular enlargement of the apical lumen, involved transcriptional activity of HNF1␤. Thus, using this sandwich culture system, we could segregate tubulogenesis of bile ducts into distinct steps and found that the PI3K/Akt pathway and HNF1␤ regulated different steps of the morphogenesis. Although the process of tubulogenesis in culture specifically resembled early bile duct formation, involvement of these two key players suggests that the sandwich culture might help us to find common principles of tubulogenesis in general. INTRODUCTIONTubules are an essential structural unit for numerous epithelial organs, such as lung, liver, and kidney. Epithelial tubes in different organs form by a wide variety of mechanisms (Hogan and Kolodziej, 2002;Lubarsky and Krasnow, 2003;Bryant and Mostov, 2008). Understanding the cellular and molecular basis of these mechanisms and discovering common principles that may underlie these diverse mechanisms is an important goal.In the liver, bile ducts are tubular structures that consist of cholangiocytes, a type of liver epithelial cell. Bile ducts provide the excretory route for bile, which is synthesized by hepatocytes, another type of liver epithelial cell. Because bile is cytotoxic, abnormal development of bile ducts, which causes the accumulation of bile inside the liver, induces hepatic injury and ultimately results in severe liver fibrosis and cirrhosis (Schmucker et al., 1990;Yoon and Gores, 2002;Paumgartner, 2006).Cholangiocytes, the epithelial component of bile ducts, differentiate from liver progenitor cells called hepatoblasts around embryonic day 15 (E15) in mice (Lemaigre, 2003). Recent reports have identified the Notch and TGF␤ signaling pathways and a transcription factor Hex, which regulate differentiation of cholangiocytes from hepatoblasts (McCright et al., 2002;Kodama et al., 2004;Clotman ...

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“…Although the exact mechanism that activates mTORC2 kinase activity is not completely understood, recent studies reported that PIP3, which accumulates when Pten is deleted, directly stimulates the kinase activity of genesis in the developing kidneys (25). However, the physiological role of PTEN in the nephron segments of developed, mature kidneys remains unclear.…”

Section: Phosphatidylinositol 3-kinase Signaling Determines Kidney Sizementioning

confidence: 99%

Phosphatidylinositol 3-kinase signaling determines kidney size

Chen¹,

Nagai²,

Chen³

et al. 2015

J. Clin. Invest.

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PTEN modulates GDNF/RET mediated chemotaxis and branching morphogenesis in the developing kidney

Cited by 57 publications

References 57 publications

Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation

Vitamin A facilitates enteric nervous system precursor migration by reducing Pten accumulation

Liver Progenitor Cells Fold Up a Cell Monolayer into a Double-layered Structure during Tubular Morphogenesis

Phosphatidylinositol 3-kinase signaling determines kidney size

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