Hepatic Notch2 deficiency leads to bile duct agenesis perinatally and secondary bile duct formation after weaning.


UNLABELLED:Notch signaling plays an acknowledged role in bile-duct development, but its involvement in cholangiocyte-fate determination remains incompletely understood. We investigated the effects of early Notch2 deletion in Notch2(fl/fl)/Alfp-Cre(tg/-) ("Notch2-cKO") and Notch2(fl/fl)/Alfp-Cre(-/-) ("control") mice. Fetal and neonatal Notch2-cKO livers were devoid of cytokeratin19 (CK19)-, Dolichos-biflorus agglutinin (DBA)-, and SOX9-positive ductal structures, demonstrating absence of prenatal cholangiocyte differentiation. Despite extensive cholestatic hepatocyte necrosis and growth retardation, mortality was only ~15%. Unexpectedly, a slow process of secondary cholangiocyte differentiation and bile-duct formation was initiated around weaning that histologically resembled the ductular reaction. Newly formed ducts varied from rare and non-connected, to multiple, disorganized tubular structures that connected to the extrahepatic bile ducts. Jaundice had disappeared in ~30% of Notch2-cKO mice by 6 months. The absence of NOTCH2 protein in postnatally differentiating cholangiocyte nuclei of Notch2-cKO mice showed that these cells had not originated from non-recombined precursor cells. Notch2 and Hnf6 mRNA levels were permanently decreased in Notch2-cKO livers. Perinatally, Foxa1, Foxa2, Hhex, Hnf1β, Cebpα and Sox9 mRNA levels were all significantly lower in Notch2-cKO than control mice, but all except Foxa2 returned to normal or increased levels after weaning, coincident with the observed secondary bile-duct formation. Interestingly, Hhex and Sox9 mRNA levels remained elevated in icteric 6 months old Notch2-cKOs, but decreased to control levels in non-icteric Notch2-cKOs, implying a key role in secondary bile-duct formation. CONCLUSION:Cholangiocyte differentiation becomes progressively less dependent on NOTCH2 signaling with age, suggesting that ductal-plate formation is dependent on NOTCH2, but subsequent cholangiocyte differentiation is not.


Dev Biol


Developmental biology


Falix FA,Weeda VB,Labruyere WT,Poncy A,de Waart DR,Hakvoort TB,Lemaigre F,Gaemers IC,Aronson DC,Lamers WH




Has Abstract


2014-12-15 00:00:00














  • Synthesis and distribution of carbohydrate chains in cleavage-stage mouse embryos carrying the t12 lethal mutation.

    abstract::Carbohydrate chains on the t12 mutant embryos were analyzed. No abnormalities of the synthesis of the carbohydrate chains were observed in the t12 homozygotes until the late morula stage, when radiolabeled carbohydrate chains were analyzed by Sephadex G-50 column chromatography. Furthermore, polarization of the Con A ...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Iwakura Y,Nozaki M

    更新日期:1988-08-01 00:00:00

  • Differential effect of activators of protein kinase C on cytoskeletal changes in mouse and hamster eggs.

    abstract::Treatment of metaphase II-arrested hamster eggs with activators of protein kinase C has been reported to promote resumption of the cell cycle, second polar body emission, and pronucleus formation (G.I. Gallicano, S.M. Schwarz, R.W. McGaughey, and D.G. Capco, 1993, Dev. Biol. 156, 94-106). In contrast, we have not obse...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Moore GD,Kopf GS,Schultz RM

    更新日期:1995-08-01 00:00:00

  • The proliferation and expansion of retinal stem cells require functional Pax6.

    abstract::Retinal stem cells (RSCs) exist as rare pigmented ciliary epithelial cells in adult mammalian eyes. We hypothesized that RSCs are at the top of the retinal cell lineage. Thus, genes expressed early in embryonic development to establish the retinal field in forebrain neuroectoderm may play important roles in RSCs. Pax6...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Xu S,Sunderland ME,Coles BL,Kam A,Holowacz T,Ashery-Padan R,Marquardt T,McInnes RR,van der Kooy D

    更新日期:2007-04-15 00:00:00

  • Role of galectin-1 in the developing mouse olfactory system.

    abstract::Primary sensory olfactory neurons reside in a neuroepithelium lining the nasal cavity and project topographically onto the surface of the olfactory bulb, a rostral extension of the telencephalon. Galectin-1, a bivalent galactose-binding vertebrate lectin, is expressed in the developing rodent olfactory system. In the ...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Puche AC,Poirier F,Hair M,Bartlett PF,Key B

    更新日期:1996-10-10 00:00:00

  • BMP receptor-activated Smads confer diverse functions during the development of the dorsal spinal cord.

    abstract::Bone Morphogenetic Proteins (BMPs) have multiple activities in the developing spinal cord: they specify the identity of the dorsal-most neuronal populations and then direct the trajectories of dorsal interneuron (dI) 1 commissural axons. How are these activities decoded by dorsal neurons to result in different cellula...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Hazen VM,Andrews MG,Umans L,Crenshaw EB 3rd,Zwijsen A,Butler SJ

    更新日期:2012-07-15 00:00:00

  • Extracellular matrix components and testicular peritubular cells influence the rate and pattern of Sertoli cell migration in vitro.

    abstract::We report the patterns of migration of Sertoli cells plated on specific substrata, and the influences of testicular peritubular cells on these processes. Data presented indicate that while peritubular cells readily spread when explanted onto Type I collagen, Sertoli cells do not. A delay of 4 to 6 days occurs after Se...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Tung PS,Fritz IB

    更新日期:1986-01-01 00:00:00

  • Specification of the mouse cardiac conduction system in the absence of Endothelin signaling.

    abstract::Coordinated contraction of the heart is essential for survival and is regulated by the cardiac conduction system. Contraction of ventricular myocytes is controlled by the terminal part of the conduction system known as the Purkinje fiber network. Lineage analyses in chickens and mice have established that the Purkinje...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Hua LL,Vedantham V,Barnes RM,Hu J,Robinson AS,Bressan M,Srivastava D,Black BL

    更新日期:2014-09-15 00:00:00

  • GATA2 regulates Wnt signaling to promote primitive red blood cell fate.

    abstract::Primitive erythropoiesis is regulated in a non cell-autonomous fashion across evolution from frogs to mammals. In Xenopus laevis, signals from the overlying ectoderm are required to induce the mesoderm to adopt an erythroid fate. Previous studies in our lab identified the transcription factor GATA2 as a key regulator ...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Mimoto MS,Kwon S,Green YS,Goldman D,Christian JL

    更新日期:2015-11-01 00:00:00

  • The role of the Suppressor of Hairy-wing insulator protein in Drosophila oogenesis.

    abstract::The Drosophila Suppressor of Hairy wing [Su(Hw)] insulator protein has an essential role in the development of the female germline. Here we investigate the function of Su(Hw) in the ovary. We show that Su(Hw) is universally expressed in somatic cells, while germ cell expression is dynamic. Robust levels accumulate in ...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Baxley RM,Soshnev AA,Koryakov DE,Zhimulev IF,Geyer PK

    更新日期:2011-08-15 00:00:00

  • Alkaline phosphatase expression in ascidian egg fragments and andromerogons.

    abstract::Alkaline phosphatase (AP) activity is expressed in the endodermal cell lineage of ascidian embryos beginning at gastrulation. AP expression is resistant to levels of actinomycin D which completely suppress the appearance of other tissue-specific enzyme and morphological markers including acetylcholinesterase (AchE), a...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Bates WR,Jeffery WR

    更新日期:1987-02-01 00:00:00

  • The Caenorhabditis elegans AHR-1 transcription complex controls expression of soluble guanylate cyclase genes in the URX neurons and regulates aggregation behavior.

    abstract::C. elegans ahr-1 is orthologous to the mammalian aryl hydrocarbon receptor, and it functions as a transcription factor to regulate the development of certain neurons. Here, we describe the role of ahr-1 in a specific behavior: the aggregation of C. elegans on lawns of bacterial food. This behavior is modulated by nutr...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Qin H,Zhai Z,Powell-Coffman JA

    更新日期:2006-10-15 00:00:00

  • Homeotic genes autonomously specify the anteroposterior subdivision of the Drosophila dorsal vessel into aorta and heart.

    abstract::The embryonic dorsal vessel in Drosophila possesses anteroposterior polarity and is subdivided into two chamber-like portions, the aorta in the anterior and the heart in the posterior. The heart portion features a wider bore as compared with the aorta and develops inflow valves (ostia) that allow the pumping of hemoly...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Lo PC,Skeath JB,Gajewski K,Schulz RA,Frasch M

    更新日期:2002-11-15 00:00:00

  • Oxygen regulates vascular endothelial growth factor-mediated vasculogenesis and tubulogenesis.

    abstract::To determine whether low oxygen is a stimulus for endothelial cell differentiation and vascular development in the kidney, we examined the effect of low oxygen on rat metanephric organ culture, a model known to recapitulate nephrogenesis in the absence of vessels. After 6 days in culture in standard (20% O2) or low ox...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Tufro-McReddie A,Norwood VF,Aylor KW,Botkin SJ,Carey RM,Gomez RA

    更新日期:1997-03-15 00:00:00

  • Chimeras between parthenogenetic or androgenetic blastomeres and normal embryos: allocation to the inner cell mass and trophectoderm.

    abstract::A series of chimeras was generated by injecting single normal, parthenogenetic, or androgenetic blastomeres carrying transgenic markers under the zona pellucida of nontransgenic eight-cell embryos. These chimeras were cultured to the blastocyst stage and sectioned, and the transgenic component was detected by in situ ...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Thomson JA,Solter D

    更新日期:1989-02-01 00:00:00

  • The mouse 14-3-3 epsilon isoform, a kinase regulator whose expression pattern is modulated in mesenchyme and neuronal differentiation.

    abstract::Kidney development is a complex, little understood process based on inductive interactions and intricate epithelial and mesenchymal morphogenesis. Here, we report the use of subtractive hybridization to clone cDNAs expressed in early nephrogenesis. cDNA made from E14.5 mouse kidney was hybridized with adult mouse live...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: McConnell JE,Armstrong JF,Hodges PE,Bard JB

    更新日期:1995-05-01 00:00:00

  • Temporal effects of Sprouty on lung morphogenesis.

    abstract::Paracrine signaling mediated by FGF-10 and the FGF-R2IIIb receptor is required for formation of the lung. To determine the temporal requirements for FGF signaling during pulmonary morphogenesis, Sprouty-4 (Spry-4), an intracellular FGF receptor antagonist, was expressed in epithelial cells of the fetal lung under cont...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Perl AK,Hokuto I,Impagnatiello MA,Christofori G,Whitsett JA

    更新日期:2003-06-01 00:00:00

  • Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect.

    abstract::Congenital bony syngnathia, a rare but severe human birth defect, is characterized by bony fusion of the mandible to the maxilla. However, the genetic mechanisms underlying this birth defect are poorly understood, largely due to limitation of available animal models. Here we present evidence that transgenic expression...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: He F,Hu X,Xiong W,Li L,Lin L,Shen B,Yang L,Gu S,Zhang Y,Chen Y

    更新日期:2014-07-15 00:00:00

  • Single embryo-resolution quantitative analysis of reporters permits multiplex spatial cis-regulatory analysis.

    abstract::Cis-regulatory modules (CRMs) control spatiotemporal gene expression patterns in embryos. While measurement of quantitative CRM activities has become efficient, measurement of spatial CRM activities still relies on slow, one-by-one methods. To overcome this bottleneck, we have developed a high-throughput method that c...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Guay CL,McQuade ST,Nam J

    更新日期:2017-02-15 00:00:00

  • Transcriptional regulation of Msx2 in the AERs of developing limbs is dependent on multiple closely spaced regulatory elements.

    abstract::In developing limb buds, Msx2 transcripts are expressed in the apical ectodermal ridge (AER) and in various regions of the limb mesenchyme. To identify DNA sequences responsible for Msx2 expression in the AER, we characterized the expression of LacZ reporter constructs driven by chicken Msx2 regulatory sequences in tr...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Cheng HC,Wang CK,Upholt WB

    更新日期:2004-06-15 00:00:00

  • PITX1 promotes chondrogenesis and myogenesis in mouse hindlimbs through conserved regulatory targets.

    abstract::The PITX1 transcription factor is expressed during hindlimb development, where it plays a critical role in directing hindlimb growth and the specification of hindlimb morphology. While it is known that PITX1 regulates hindlimb formation, in part, through activation of the Tbx4 gene, other transcriptional targets remai...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Wang JS,Infante CR,Park S,Menke DB

    更新日期:2018-02-01 00:00:00

  • Evolutionary developmental transition from median to paired morphology of vertebrate fins: Perspectives from twin-tail goldfish.

    abstract::Vertebrate morphology has been evolutionarily modified by natural and/or artificial selection. The morphological variation of goldfish is a representative example. In particular, the twin-tail strain of ornamental goldfish shows highly diverged anal and caudal fin morphology: bifurcated anal and caudal fins. Recent mo...

    journal_title:Developmental biology

    pub_type: 杂志文章,评审


    authors: Abe G,Ota KG

    更新日期:2017-07-15 00:00:00

  • Complement component C3aR constitutes a novel regulator for chick eye morphogenesis.

    abstract::Complement components have been implicated in a wide variety of functions including neurogenesis, proliferation, cell migration, differentiation, cancer, and more recently early development and regeneration. Following our initial observations indicating that C3a/C3aR signaling induces chick retina regeneration, we ana...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Grajales-Esquivel E,Luz-Madrigal A,Bierly J,Haynes T,Reis ES,Han Z,Gutierrez C,McKinney Z,Tzekou A,Lambris JD,Tsonis PA,Del Rio-Tsonis K

    更新日期:2017-08-01 00:00:00

  • Mifepristone-inducible LexPR system to drive and control gene expression in transgenic zebrafish.

    abstract::Effective transgenesis methods have been successfully employed in many organisms including zebrafish. However, accurate spatiotemporal control of transgene expression is still difficult to achieve. Here we describe a system for chemical-inducible gene expression and demonstrate its feasibility for generating transgeni...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Emelyanov A,Parinov S

    更新日期:2008-08-01 00:00:00

  • A growth-promoting influence from the mesonephros during limb outgrowth.

    abstract::It has been suggested that the mesonephros has a role in normal limb development. This hypothesis was directly tested by removing the mesonephros adjacent to the presumptive limb region of stage 12-18 chick embryos using microsurgery or laser ablation. The experimental manipulation resulted in reduced limb outgrowth o...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Geduspan JS,Solursh M

    更新日期:1992-05-01 00:00:00

  • Activation of pmar1 controls specification of micromeres in the sea urchin embryo.

    abstract::pmar1 is a transcription factor in the paired class homeodomain family that was identified and found to be transcribed in micromeres beginning at the fourth cleavage of sea urchin development [Dev. Biol. 246 (2002), 209]. Based on in situ data, molecular perturbation studies, and QPCR data, the recently published gene...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Oliveri P,Davidson EH,McClay DR

    更新日期:2003-06-01 00:00:00

  • Peanut agglutinin and chondroitin-6-sulfate are molecular markers for tissues that act as barriers to axon advance in the avian embryo.

    abstract::Axon outgrowth between the spinal cord and the hindlimb of the chick embryo is constrained by three tissues that border axon pathways. Growth cones turn to avoid the posterior sclerotome, perinotochordal mesenchyme, and pelvic girdle precursor during normal development and after experimental manipulation. We wanted to...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Oakley RA,Tosney KW

    更新日期:1991-09-01 00:00:00

  • The armadillo homologs beta-catenin and plakoglobin are differentially expressed during early development of Xenopus laevis.

    abstract::Plakoglobin and beta-catenin are cytoplasmic proteins associated with the intracellular plaques of cell adhesive junctions. While plakoglobin is present in both adherens junctions and desmosomes, beta-catenin is associated with the cadherins that accumulate only in adherens junctions. Both beta-catenin and plakoglobin...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: DeMarais AA,Moon RT

    更新日期:1992-10-01 00:00:00

  • PDGFB regulates the development of the labyrinthine layer of the mouse fetal placenta.

    abstract::PDGFB is a growth factor which is vital for the completion of normal prenatal development. In this study, we report the phenotypic analysis of placentas from mouse conceptuses that lack a functional PDGFB or PDGFRbeta gene. Placentas of both types of mutant exhibit changes in the labyrinthine layer, including dilated ...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Ohlsson R,Falck P,Hellström M,Lindahl P,Boström H,Franklin G,Ahrlund-Richter L,Pollard J,Soriano P,Betsholtz C

    更新日期:1999-08-01 00:00:00

  • Mesodermal guidance of pioneer axon growth.

    abstract::Pioneer axons in insect legs are experimentally accessible model systems for the molecular identification and cellular localization of guidance cues regulating the path of axon growth. A detailed study of the Fe2 pioneer axons in the legs of the cockroach was performed to examine the diversity of guidance mechanisms. ...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Rajan I,Denburg JL

    更新日期:1997-10-15 00:00:00

  • Sperm-induced Ca(2+) oscillations in mouse oocytes and eggs can be mimicked by photolysis of caged inositol 1,4,5-trisphosphate: evidence to support a continuous low level production of inositol 1, 4,5-trisphosphate during mammalian fertilization.

    abstract::During mouse fertilization the spermatozoon induces a series of low-frequency long-lasting Ca(2+) oscillations. It is generally accepted that these oscillations are due to Ca(2+) release through the inositol 1,4,5-trisphosphate (InsP(3)) receptor. However, InsP(3) microinjection does not mimic sperm-induced Ca(2+) osc...

    journal_title:Developmental biology

    pub_type: 杂志文章


    authors: Jones KT,Nixon VL

    更新日期:2000-09-01 00:00:00