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Kreidberg, Jordan

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Kreidberg

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Jordan

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Kreidberg, Jordan
Author's Publications: search.filters.isAuthorOfPublication.1f5f307d-7bfc-4f41-bac7-a618f0d0fb17

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    Bmp7 Maintains Undifferentiated Kidney Progenitor Population and Determines Nephron Numbers at Birth
    (Public Library of Science, 2013) Tomita, Mayumi; Asada, Misako; Asada, Nariaki; Nakamura, Jin; Oguchi, Akiko; Higashi, Atsuko Y.; Endo, Shuichiro; Robertson, Elizabeth; Kimura, Takeshi; Kita, Toru; Economides, Aris N.; Kreidberg, Jordan; Yanagita, Motoko
    The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth.
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    GPR56 Functions Together with α3β1 Integrin in Regulating Cerebral Cortical Development
    (Public Library of Science, 2013) Jeong, Sung-Jin; Luo, Rong; Singer, Kathleen; Giera, Stefanie; Kreidberg, Jordan; Kiyozumi, Daiji; Shimono, Chisei; Sekiguchi, Kiyotoshi; Piao, Xianhua
    Loss of function mutations in GPR56, which encodes a G protein-coupled receptor, cause a specific human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Studies from BFPP postmortem brain tissue and Gpr56 knockout mice have previously showed that GPR56 deletion leads to breaches in the pial basement membrane (BM) and neuronal ectopias during cerebral cortical development. Since α3β1 integrin also plays a role in pial BM assembly and maintenance, we evaluated whether it functions together with GPR56 in regulating the same developmental process. We reveal that loss of α3 integrin enhances the cortical phenotype associated with Gpr56 deletion, and that neuronal overmigration through a breached pial BM occurs earlier in double knockout than in Gpr56 single knockout mice. These observations provide compelling evidence of the synergism of GPR56 and α3β1 integrin in regulating the development of cerebral cortex.
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    Systems Biology Approach to Identify Transcriptome Reprogramming and Candidate MicroRNA Targets during the Progression of Polycystic Kidney Disease
    (BioMed Central, 2011) Pandey, Priyanka; Qin, Shan; Ho, Jacqueline; Zhou, Jing; Kreidberg, Jordan
    Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation throughout the kidney parenchyma. It is caused by mutations in either of two genes, \(PKD1\) and \(PKD2\). Mice that lack functional \(Pkd1 (Pkd1^{-/-})\), develop rapidly progressive cystic disease during embryogenesis, and serve as a model to study human ADPKD. Genome wide transcriptome reprogramming and the possible roles of micro-RNAs (miRNAs) that affect the initiation and progression of cyst formation in the \(Pkd1^{-/-}\) have yet to be studied. miRNAs are small, regulatory non-coding RNAs, implicated in a wide spectrum of biological processes. Their expression levels are altered in several diseases including kidney cancer, diabetic nephropathy and PKD. Results: We examined the molecular pathways that modulate renal cyst formation and growth in the \(Pkd1^{-/-}\) model by performing global gene-expression profiling in embryonic kidneys at days 14.5 and 17.5. Gene Ontology and gene set enrichment analysis were used to identify overrepresented signaling pathways in \(Pkd1^{-/-}\) kidneys. We found dysregulation of developmental, metabolic, and signaling pathways (e.g. Wnt, calcium, \(TGF-\beta\) and MAPK) in \(Pkd^{-/-}\) kidneys. Using a comparative transcriptomics approach, we determined similarities and differences with human ADPKD: ~50% overlap at the pathway level among the mis-regulated pathways was observed. By using computational approaches (TargetScan, miRanda, microT and miRDB), we then predicted miRNAs that were suggested to target the differentially expressed mRNAs. Differential expressions of 9 candidate miRNAs, miRs-10a, -30a-5p, -96, -126-5p, -182, -200a, -204, -429 and -488, and 16 genes were confirmed by qPCR. In addition, 14 candidate miRNA:mRNA reciprocal interactions were predicted. Several of the highly regulated genes and pathways were predicted as targets of miRNAs. Conclusions: We have described global transcriptional reprogramming during the progression of PKD in the \(Pkd1^{-/-}\) model. We propose a model for the cascade of signaling events involved in cyst formation and growth. Our results suggest that several miRNAs may be involved in regulating signaling pathways in ADPKD. We further describe novel putative miRNA:mRNA signatures in ADPKD, which will provide additional insights into the pathogenesis of this common genetic disease in humans.