The GDNF Target Vsnl1 Marks the Ureteric Tip

Ola, Roxana; Jakobson, Madis; Kvist, Jouni; Perälä, Nina; Kuure, Satu; Braunewell, Karl-Heinz; Bridgewater, Darren; Rosenblum, Norman D.; Chilov, Dmitri; Immonen, Tiina; Sainio, Kirsi; Sariola, Hannu

doi:10.1681/asn.2010030316

Cited by 25 publications

(31 citation statements)

References 65 publications

(75 reference statements)

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“…Identification of GDNF/RET targets recently revealed several interesting candidates for mediating these functions [33], [34] but the intracellular cascades regulating the expression changes remain to be solved. Similarly to previous chemical inhibition studies [33], we saw that the expression of transcription factors Etv4 and - 5 was normal whenever UBs were present and thus does not require MAPK activity.…”

Section: Discussionmentioning

confidence: 99%

Mitogen-Activated Protein Kinase (MAPK) Pathway Regulates Branching by Remodeling Epithelial Cell Adhesion

et al. 2014

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Although the growth factor (GF) signaling guiding renal branching is well characterized, the intracellular cascades mediating GF functions are poorly understood. We studied mitogen-activated protein kinase (MAPK) pathway specifically in the branching epithelia of developing kidney by genetically abrogating the pathway activity in mice lacking simultaneously dual-specificity protein kinases Mek1 and Mek2. Our data show that MAPK pathway is heterogeneously activated in the subset of G1- and S-phase epithelial cells, and its tissue-specific deletion results in severe renal hypodysplasia. Consequently to the deletion of Mek1/2, the activation of ERK1/2 in the epithelium is lost and normal branching pattern in mutant kidneys is substituted with elongation-only phenotype, in which the epithelium is largely unable to form novel branches and complex three-dimensional patterns, but able to grow without primary defects in mitosis. Cellular characterization of double mutant epithelium showed increased E-cadherin at the cell surfaces with its particular accumulation at baso-lateral locations. This indicates changes in cellular adhesion, which were revealed by electron microscopic analysis demonstrating intercellular gaps and increased extracellular space in double mutant epithelium. When challenged to form monolayer cultures, the mutant epithelial cells were impaired in spreading and displayed strong focal adhesions in addition to spiky E-cadherin. Inhibition of MAPK activity reduced paxillin phosphorylation on serine 83 while remnants of phospho-paxillin, together with another focal adhesion (FA) protein vinculin, were augmented at cell surface contacts. We show that MAPK activity is required for branching morphogenesis, and propose that it promotes cell cycle progression and higher cellular motility through remodeling of cellular adhesions.

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Section: Discussionmentioning

confidence: 99%

Mitogen-Activated Protein Kinase (MAPK) Pathway Regulates Branching by Remodeling Epithelial Cell Adhesion

et al. 2014

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“…Thus, it is conceivable that Ang II may stimulate UB cell movement, in part, via upregulation of Etv4 / Etv5 . Vsnl1 , which encodes a calcium-sensing protein and is expressed exclusively in the UB tip domain, is upregulated by both Ang II and GDNF (Ola et al, 2011). Because UB tip cells contain elevated intracellular calcium levels (Ola et al, 2011) and activation of calcium signaling induces actin cytoskeleton reorganization in MDCK cells (Miranda et al, 2010), Ang II-induced upregulation of Vsnl1 expression in the UB may act to promote expansion of the ampulla by creating wedge-shaped cells through an apical purse-string mechanism (Meyer et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II stimulates in vitro branching morphogenesis of the isolated ureteric bud

Song

Preston

Yosypiv

2011

Mechanisms of Development

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Mutations in the renin-angiotensin system (RAS) genes are associated with congenital anomalies of the kidney and urinary tract (CAKUT). As angiotensin (Ang) II, the principal effector peptide growth factor of the RAS, stimulates ureteric bud (UB) branching in whole intact embryonic (E) metanephroi, defects in UB morphogenesis may be causally linked to CAKUT observed under conditions of disrupted RAS. In the present study, using the isolated intact UB (iUB) assay, we tested the hypothesis that Ang II stimulates UB morphogenesis by directly acting on the UB, identified Ang II target genes in the iUB by microarray and examined the effect of Ang II on UB cell migration in vitro. We show that isolated E11.5 mouse iUBs express Ang II AT1 and AT2 receptor mRNA. Treatment of E11.5 iUBs grown in collagen matrix gels with Ang II (10−5 M) increases the number of iUB tips after 48 hours of culture compared to control (4.8±0.4 vs. 2.4±0.2, p<0.01). A number of genes required for UB branching as well as novel genes whose role in UB development is currently unknown are targets of Ang II signaling in the iUB. In addition, Ang II increases UB cell migration (346±5.1 vs. 275±4.4, p<0.01 ) in vitro. In summary, Ang II stimulates UB cell migration and directly induces morphogenetic response in the iUB. We conclude that Ang II-regulated genes in the iUB may be important mediators of Ang II-induced UB branching. We hypothesize that Ang II-dependent cell movements play an important role in UB branching morphogenesis.

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“…Using these criteria, we identified six genes that may be associated with distinct morphologies at the anterior region of the pectoral fins of R. bonasus and L. erinacea (Table 3). Dkk1 is a known inhibitor of the Wnt signaling pathway (Glinka et al, 1998;Fedi et al, 1999;Niida et al, 2004), while Vsnl1 downregulates β-catenin-an important component of canonical Wnt signaling-in mouse kidneys (Ola et al, 2011). These genes are upregulated in R. bonasus but not L. erinacea and may have a role in notch development by inhibiting AERsignaling in this region.…”

Section: Modified Gene Expression Patterns Associated With Unique Mylmentioning

confidence: 99%

How the Devil Ray Got Its Horns: The Evolution and Development of Cephalic Lobes in Myliobatid Stingrays (Batoidea: Myliobatidae)

et al. 2018

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Manta rays and their relatives of the family Myliobatidae have pectoral fins that have been modified for underwater flight, as well as a pair of fleshy projections at the anterior of the body called cephalic lobes, which are specialized for feeding. As a unique trait with a dedicated function, cephalic lobes offer an excellent opportunity to elucidate the processes by which diverse body plans and features evolve. To shed light on the morphological development and genetic underpinnings of cephalic lobes, we examined paired fin development in cownose rays, which represent the sister taxon to manta rays in the genus Mobula. We find that cephalic lobes develop as anterior pectoral fin domains and lack independent posterior patterning by 5 ′ HoxD genes and Shh, indicating that cephalic lobes are not independent appendages but rather are modified pectoral fin domains. In addition, by leveraging interspecies comparative transcriptomics and domain-specific RNA-sequencing, we identify shared expression of anterior patterning genes, including Alx1, Alx4, Pax9, Hoxa13, Hoxa2, and Hoxd4, in the pectoral fins of cownose ray (Rhinoptera bonasus) and little skate (Leucoraja erinacea), providing evidence supporting homology between the cephalic lobes of myliobatids and the anterior pectoral fins of skates. We also suggest candidate genes that may be involved in development of myliobatid-specific features, including Omd, which is likely associated with development of thick anterior pectoral fin radials of myliobatids, and Dkk1, which may inhibit tissue outgrowth at the posterior boundary of the developing cephalic lobes. Finally, we observe that cephalic lobes share a surprising number of developmental similarities with another paired fin modification: the claspers of male cartilaginous fishes, including enrichment of Hand2, Hoxa13, and androgen receptor. These results suggest that cephalic lobes may have evolved by co-opting developmental pathways that specify novel domains in paired fins. Taken together, these data on morphological development and comparative gene expression patterns illustrate how distinct body plans and seemingly novel features can arise via subtle changes to existing developmental pathways.

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The GDNF Target Vsnl1 Marks the Ureteric Tip

Cited by 25 publications

References 65 publications

Mitogen-Activated Protein Kinase (MAPK) Pathway Regulates Branching by Remodeling Epithelial Cell Adhesion

Mitogen-Activated Protein Kinase (MAPK) Pathway Regulates Branching by Remodeling Epithelial Cell Adhesion

Angiotensin II stimulates in vitro branching morphogenesis of the isolated ureteric bud

How the Devil Ray Got Its Horns: The Evolution and Development of Cephalic Lobes in Myliobatid Stingrays (Batoidea: Myliobatidae)

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