Two novel EGFP insertion alleles reveal unique aspects of Pax2 function in embryonic and adult kidneys

Soofi, Abdul; Levitan, Inna; Dressler, Gregory R.

doi:10.1016/j.ydbio.2012.02.032

Cited by 39 publications

(43 citation statements)

References 44 publications

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“…Similarly, Pax2 plays a role in epithelial maintenance during kidney development. Mouse Pax2 mutants display severe renal defects resulting from loss of epithelial structure in the nephric duct, accompanied by formation of irregular outgrowths and increased cell motility (45,46).…”

Section: Discussionmentioning

confidence: 99%

Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle

Kantarci

Gerberding

Riley

2016

Proc. Natl. Acad. Sci. U.S.A.

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Neurons of the Statoacoustic Ganglion (SAG), which innervate the inner ear, originate as neuroblasts in the floor of the otic vesicle and subsequently delaminate and migrate toward the hindbrain before completing differentiation. In all vertebrates, locally expressed Fgf initiates SAG development by inducing expression of Neurogenin1 (Ngn1) in the floor of the otic vesicle. However, not all Ngn1-positive cells undergo delamination, nor has the mechanism controlling SAG delamination been elucidated. Here we report that Goosecoid (Gsc), best known for regulating cellular dynamics in the Spemann organizer, regulates delamination of neuroblasts in the otic vesicle. In zebrafish, Fgf coregulates expression of Gsc and Ngn1 in partially overlapping domains, with delamination occurring primarily in the zone of overlap. Loss of Gsc severely inhibits delamination, whereas overexpression of Gsc greatly increases delamination. Comisexpression of Ngn1 and Gsc induces ectopic delamination of some cells from the medial wall of the otic vesicle but with a low incidence, suggesting the action of a local inhibitor. The medial marker Pax2a is required to restrict the domain of gsc expression, and misexpression of Pax2a is sufficient to block delamination and fully suppress the effects of Gsc. The opposing activities of Gsc and Pax2a correlate with repression or up-regulation, respectively, of E-cadherin (cdh1). These data resolve a genetic mechanism controlling delamination of otic neuroblasts. The data also elucidate a developmental role for Gsc consistent with a general function in promoting epithelial-to-mesenchymal transition (EMT).

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Section: Discussionmentioning

confidence: 99%

Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle

Kantarci

Gerberding

Riley

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Section ISH was performed as previously described (Mendelsohn et al, 1999;Di Giacomo et al, 2006). Detection of Hox6 mRNA was done using probes generated against the 3′ untranslated region of Hoxa6, Hoxb6 and Hoxc6 or against the Neo r cassette as previously (Miller et al, 2012;Soofi et al, 2012;Ranghini and Dressler, 2015).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Mesenchymal Hox6 function is required for pancreatic endocrine cell differentiation

et al. 2015

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Despite significant advances in our understanding of pancreatic endocrine cell development, the function of the pancreatic mesodermal niche in this process is poorly understood. Here we report a novel role for mouse Hox6 genes in pancreatic organogenesis. Hox6 genes are expressed exclusively in the mesoderm of the developing pancreas. Genetic loss of all three Hox6 paralogs (Hoxa6, Hoxb6 and Hoxc6) leads to a dramatic loss of endoderm-derived endocrine cells, including insulin-secreting β-cells, and to mild delays and disruptions in pancreatic branching and exocrine differentiation. Ngn3-expressing pan-endocrine progenitor cells are specified normally in Hox6 mutant pancreata, but fail to mature into hormone-producing cells. Reduced expression of Wnt5a is observed in mutant pancreatic mesenchyme, leading to subsequent loss of expression of the crucial Wnt inhibitors Sfrp3 and Dkk1 in endocrine progenitor cells. These results reveal a key role for Hox6 genes in establishing Wnt mesenchymal-epithelial crosstalk in pancreatic development.

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“…Immunofluorescence detection was done using modifications of published protocols. 30 Paraffin sections of 5 mm were rehydrated and stained with mouse anti-Myc-KCP (9E10; BaCO) or monoclonal anti-Myc-FITC (Sigma), rabbit antiMyc-KCP, rabbit anti-Laminin (L9393; Sigma), monoclonal anti-a-SMACy3 conjugated (catalog # C6193; Sigma), rabbit anti-collagen IV (catalog # AB756P; Chemicon), or goat anti-Kim1 (anti-mTIM1, catalog # AF1817; R&D Systems). Images were collected using an Olympus DP72 camera.…”

Section: Immunostainingmentioning

confidence: 99%

Kielin/Chordin-Like Protein Attenuates both Acute and Chronic Renal Injury

Soofi

Zhang

Dressler

2013

Journal of the American Society of Nephrology

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The secreted kielin/chordin-like (KCP) protein, one of a family of cysteine-rich proteins, suppresses TGF-b signaling by sequestering the ligand from its receptor, but it enhances bone morphogenetic protein (BMP) signaling by promoting ligand-receptor interactions. Given the critical roles for TGF-b and BMP proteins in enhancing or suppressing renal interstitial fibrosis, respectively, we examined whether secreted KCP could attenuate renal fibrosis in mouse models of chronic and acute disease. Transgenic mice that express KCP in adult kidneys showed significantly less expression of collagen IV, a-smooth muscle actin, and other markers of disease progression in the unilateral ureteral obstruction model of renal interstitial fibrosis. In the folic acid nephrotoxicity model of acute tubular necrosis, mice expressing KCP survived high doses of folic acid that were lethal for wild-type mice. With a lower dose of folic acid, mice expressing KCP exhibited improved renal recovery compared with wild-type mice. Thus, these data suggest that extracellular regulation of the TGF-b/BMP signaling axis by KCP, and by extension possibly other cysteine-rich domain proteins, can attenuate both acute and chronic renal injury.

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Two novel EGFP insertion alleles reveal unique aspects of Pax2 function in embryonic and adult kidneys

Cited by 39 publications

References 44 publications

Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle

Spemann organizer gene Goosecoid promotes delamination of neuroblasts from the otic vesicle

Mesenchymal Hox6 function is required for pancreatic endocrine cell differentiation

Kielin/Chordin-Like Protein Attenuates both Acute and Chronic Renal Injury

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