Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 6 of 6

Publication Record


Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism.
Ahnfelt-Rønne J, Jørgensen MC, Klinck R, Jensen JN, Füchtbauer EM, Deering T, MacDonald RJ, Wright CV, Madsen OD, Serup P
(2012) Development 139: 33-45
MeSH Terms: Animals, Basic Helix-Loop-Helix Transcription Factors, Bromodeoxyuridine, Calcium-Binding Proteins, Chromatin Immunoprecipitation, Galactosides, Gene Expression Regulation, Homeodomain Proteins, Immunohistochemistry, Indoles, Intercellular Signaling Peptides and Proteins, Mice, Mice, Transgenic, Nerve Tissue Proteins, Pancreas, Pancreatic Polypeptide-Secreting Cells, Stem Cells, Transcription Factor HES-1, Transcription Factors
Show Abstract · Added November 6, 2013
Neurog3-induced Dll1 expression in pancreatic endocrine progenitors ostensibly activates Hes1 expression via Notch and thereby represses Neurog3 and endocrine differentiation in neighboring cells by lateral inhibition. Here we show in mouse that Dll1 and Hes1 expression deviate during regionalization of early endoderm, and later during early pancreas morphogenesis. At that time, Ptf1a activates Dll1 in multipotent pancreatic progenitor cells (MPCs), and Hes1 expression becomes Dll1 dependent over a brief time window. Moreover, Dll1, Hes1 and Dll1/Hes1 mutant phenotypes diverge during organ regionalization, become congruent at early bud stages, and then diverge again at late bud stages. Persistent pancreatic hypoplasia in Dll1 mutants after eliminating Neurog3 expression and endocrine development, together with reduced proliferation of MPCs in both Dll1 and Hes1 mutants, reveals that the hypoplasia is caused by a growth defect rather than by progenitor depletion. Unexpectedly, we find that Hes1 is required to sustain Ptf1a expression, and in turn Dll1 expression in early MPCs. Our results show that Ptf1a-induced Dll1 expression stimulates MPC proliferation and pancreatic growth by maintaining Hes1 expression and Ptf1a protein levels.
2 Communities
2 Members
5 Resources
19 MeSH Terms
FGF/EGF signaling regulates the renewal of early nephron progenitors during embryonic development.
Brown AC, Adams D, de Caestecker M, Yang X, Friesel R, Oxburgh L
(2011) Development 138: 5099-112
MeSH Terms: Adaptor Proteins, Signal Transducing, Animals, Apoptosis Regulatory Proteins, Cell Differentiation, Cell Lineage, Cells, Cultured, Epidermal Growth Factor, Fibroblast Growth Factors, Galactosides, In Situ Nick-End Labeling, Indoles, Membrane Proteins, Mice, Microscopy, Fluorescence, Nephrons, Nuclear Proteins, Phosphatidylinositol 3-Kinases, Phosphoproteins, Polymerase Chain Reaction, Receptor Protein-Tyrosine Kinases, Signal Transduction, Trans-Activators, ras Proteins
Show Abstract · Added March 20, 2014
Recent studies indicate that nephron progenitor cells of the embryonic kidney are arranged in a series of compartments of an increasing state of differentiation. The earliest progenitor compartment, distinguished by expression of CITED1, possesses greater capacity for renewal and differentiation than later compartments. Signaling events governing progression of nephron progenitor cells through stages of increasing differentiation are poorly understood, and their elucidation will provide key insights into normal and dysregulated nephrogenesis, as well as into regenerative processes that follow kidney injury. In this study, we found that the mouse CITED1(+) progenitor compartment is maintained in response to receptor tyrosine kinase (RTK) ligands that activate both FGF and EGF receptors. This RTK signaling function is dependent on RAS and PI3K signaling but not ERK. In vivo, RAS inactivation by expression of sprouty 1 (Spry1) in CITED1(+) nephron progenitors results in loss of characteristic molecular marker expression and in increased death of progenitor cells. Lineage tracing shows that surviving Spry1-expressing progenitor cells are impaired in their subsequent epithelial differentiation, infrequently contributing to epithelial structures. These findings demonstrate that the survival and developmental potential of cells in the earliest embryonic nephron progenitor cell compartment are dependent on FGF/EGF signaling through RAS.
2 Communities
1 Members
0 Resources
23 MeSH Terms
Conditional gene targeting in mouse pancreatic ß-Cells: analysis of ectopic Cre transgene expression in the brain.
Wicksteed B, Brissova M, Yan W, Opland DM, Plank JL, Reinert RB, Dickson LM, Tamarina NA, Philipson LH, Shostak A, Bernal-Mizrachi E, Elghazi L, Roe MW, Labosky PA, Myers MG, Gannon M, Powers AC, Dempsey PJ
(2010) Diabetes 59: 3090-8
MeSH Terms: Animals, Brain, Crosses, Genetic, Estrogen Antagonists, Female, Galactosides, Gene Targeting, Genes, Reporter, Immunoglobulin G, Immunohistochemistry, Insulin, Insulin-Secreting Cells, Integrases, Leptin, Male, Mice, Mice, Transgenic, Reverse Transcriptase Polymerase Chain Reaction, Swine, Tamoxifen
Show Abstract · Added January 6, 2014
OBJECTIVE - Conditional gene targeting has been extensively used for in vivo analysis of gene function in β-cell biology. The objective of this study was to examine whether mouse transgenic Cre lines, used to mediate β-cell- or pancreas-specific recombination, also drive Cre expression in the brain.
RESEARCH DESIGN AND METHODS - Transgenic Cre lines driven by Ins1, Ins2, and Pdx1 promoters were bred to R26R reporter strains. Cre activity was assessed by β-galactosidase or yellow fluorescent protein expression in the pancreas and the brain. Endogenous Pdx1 gene expression was monitored using Pdx1(tm1Cvw) lacZ knock-in mice. Cre expression in β-cells and co-localization of Cre activity with orexin-expressing and leptin-responsive neurons within the brain was assessed by immunohistochemistry.
RESULTS - All transgenic Cre lines examined that used the Ins2 promoter to drive Cre expression showed widespread Cre activity in the brain, whereas Cre lines that used Pdx1 promoter fragments showed more restricted Cre activity primarily within the hypothalamus. Immunohistochemical analysis of the hypothalamus from Tg(Pdx1-cre)(89.1Dam) mice revealed Cre activity in neurons expressing orexin and in neurons activated by leptin. Tg(Ins1-Cre/ERT)(1Lphi) mice were the only line that lacked Cre activity in the brain.
CONCLUSIONS - Cre-mediated gene manipulation using transgenic lines that express Cre under the control of the Ins2 and Pdx1 promoters are likely to alter gene expression in nutrient-sensing neurons. Therefore, data arising from the use of these transgenic Cre lines must be interpreted carefully to assess whether the resultant phenotype is solely attributable to alterations in the islet β-cells.
3 Communities
5 Members
0 Resources
20 MeSH Terms
Interactions between areas I and II direct pdx-1 expression specifically to islet cell types of the mature and developing pancreas.
Van Velkinburgh JC, Samaras SE, Gerrish K, Artner I, Stein R
(2005) J Biol Chem 280: 38438-44
MeSH Terms: Animals, Animals, Newborn, Base Sequence, Binding Sites, Cell Differentiation, Cell Line, Cell Nucleus, Chromatin, Chromatin Immunoprecipitation, DNA Mutational Analysis, Enhancer Elements, Genetic, Galactosides, Homeodomain Proteins, Humans, Immunohistochemistry, Indoles, Insulin, Insulinoma, Islets of Langerhans, Lac Operon, Mice, Molecular Sequence Data, NIH 3T3 Cells, Pancreas, Protein Binding, Protein Structure, Tertiary, Recombinant Fusion Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transfection, Transgenes, Zebrafish Proteins
Show Abstract · Added August 13, 2010
PDX-1 regulates transcription of genes involved in islet beta cell function and pancreas development. Islet-specific expression is controlled by 5'-flanking sequences from base pair (bp) -2917 to -1918 in transgenic experiments, which encompasses both conserved (i.e. Area I (bp -2761/-2457), Area II (bp -2153/-1923)) and non-conserved pdx-1 sequences. However, only an Area II-driven transgene is independently active in vivo, albeit in only a fraction of islet PDX-1-producing cells. Our objective was to identify the sequences within the -2917/-1918-bp region that act in conjunction with Area II to allow comprehensive expression in islet PDX-1(+) cells. In cell line-based transfection assays, only Area I effectively potentiated Area II activity. Both Area I and Area II functioned in an orientation-independent manner, whereas synergistic, enhancer-like activation was uniquely found with duplicated Area II. Chimeras of Area II and the generally active SV40 enhancer or the beta cell-specific insulin enhancer suggested that islet cell-enriched activators were necessary for Area I activation, because Area II-mediated stimulation was reduced by the SV40 enhancer and activated by the insulin enhancer. Several conserved sites within Area I were important in Area I/Area II activation, with binding at bp -2614/-2609 specifically controlled by Nkx2.2, an insulin gene regulator that is required for terminal beta cell differentiation. The ability of Area I to modulate Area II activation was also observed in vivo, as an Area I/Area II-driven transgene recapitulated the endogenous pdx-1 expression pattern in developing and adult islet cells. These results suggest that Area II is a central pdx-1 control region, whose islet cell activity is uniquely modified by Area I regulatory factors.
1 Communities
0 Members
0 Resources
33 MeSH Terms
Analysis of SOX10 function in neural crest-derived melanocyte development: SOX10-dependent transcriptional control of dopachrome tautomerase.
Potterf SB, Mollaaghababa R, Hou L, Southard-Smith EM, Hornyak TJ, Arnheiter H, Pavan WJ
(2001) Dev Biol 237: 245-57
MeSH Terms: Animals, Animals, Genetically Modified, Cell Lineage, Cells, Cultured, DNA-Binding Proteins, Galactosides, Gene Expression Regulation, Developmental, Genotype, Heterozygote, High Mobility Group Proteins, Homozygote, Immunohistochemistry, In Situ Hybridization, Indoles, Intramolecular Oxidoreductases, Luciferases, Melanocytes, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microphthalmia-Associated Transcription Factor, Mutation, Neural Crest, Pigmentation, Plasmids, SOXE Transcription Factors, Time Factors, Transcription Factors, Transcription, Genetic, Transfection
Show Abstract · Added February 25, 2015
SOX10 is a high-mobility-group transcription factor that plays a critical role in the development of neural crest-derived melanocytes. At E11.5, mouse embryos homozygous for the Sox10(Dom) mutation entirely lack neural crest-derived cells expressing the lineage marker KIT, MITF, or DCT. Moreover, neural crest cell cultures derived from homozygous embryos do not give rise to pigmented cells. In contrast, in Sox10(Dom) heterozygous embryos, melanoblasts expressing KIT and MITF do occur, albeit in reduced numbers, and pigmented cells eventually develop in nearly normal numbers both in culture and in vivo. Intriguingly, however, Sox10(Dom)/+ melanoblasts transiently lack Dct expression both in culture and in vivo, suggesting that during a critical developmental period SOX10 may serve as a transcriptional activator of Dct. Indeed, we found that SOX10 and DCT colocalized in early melanoblasts and that SOX10 is capable of transactivating the Dct promoter in vitro. Our data suggest that during early melanoblast development SOX10 acts as a critical transactivator of Dct, that MITF, on its own, is insufficient to stimulate Dct expression, and that delayed onset of Dct expression is not deleterious to the melanocyte lineage.
0 Communities
1 Members
0 Resources
30 MeSH Terms
Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation.
Wu X, Wu J, Huang J, Powell WC, Zhang J, Matusik RJ, Sangiorgi FO, Maxson RE, Sucov HM, Roy-Burman P
(2001) Mech Dev 101: 61-9
MeSH Terms: Alleles, Animals, Crosses, Genetic, Epithelium, Female, Galactosides, Immunohistochemistry, Indoles, Integrases, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Mice, Transgenic, Ovary, Polymerase Chain Reaction, Promoter Regions, Genetic, Prostate, Prostatic Neoplasms, Rats, Receptors, Retinoic Acid, Reverse Transcriptase Polymerase Chain Reaction, Testis, Time Factors, Tissue Distribution, Transgenes, Viral Proteins
Show Abstract · Added June 11, 2010
To facilitate the elucidation of the genetic events that may play an important role in the development or tumorigenesis of the prostate gland, we have generated a transgenic mouse line with prostate-specific expression of Cre recombinase. This line, named PB-Cre4, carries the Cre gene under the control of a composite promoter, ARR2PB which is a derivative of the rat prostate-specific probasin (PB) promoter. Based on RT-PCR detection of Cre mRNA in PB-Cre4 mice or Cre-mediated activation of LacZ activity in PB-Cre4/R26R double transgenic mice, it is conclusively demonstrated that Cre expression is post-natal and prostatic epithelium-specific. Although the Cre recombination is detected in all lobes of the mouse prostate, there is a significant difference in expression levels between the lobes, being highest in the lateral lobe, followed by the ventral, and then the dorsal and anterior lobes. Besides the prostate gland, no other tissues of the adult PB-Cre4 mice demonstrate significant Cre expression, except for a few scattered areas in the gonads and the stroma of the seminal vesicle. By crossing the PB-Cre4 animals with floxed RXRalpha allelic mice, we demonstrate that mice, whose conventional knockout of this gene is lethal in embryogenesis, could be propagated with selective inactivation of RXRalpha in the prostate. Taken together, the results show that the PB-Cre4 mice have high levels of Cre expression and a high penetrance in the prostatic epithelium. The PB-Cre4 mice will be a useful resource for genetic-based studies on prostate development and prostatic disease.
1 Communities
1 Members
0 Resources
28 MeSH Terms