Article

Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2.

Laboratory of Molecular Pathology, Department of Pathology, Dallas, TX 75390-9072, USA.
Molecular and Cellular Biology (impact factor: 5.53). 07/2007; 27(12):4454-64. DOI:10.1128/MCB.00133-07 pp.4454-64
Source: PubMed

ABSTRACT Gradients of Wnt/beta-catenin signaling coordinate development and physiological homeostasis in metazoan animals. Proper embryonic development of the fruit fly Drosophila melanogaster requires the Naked cuticle (Nkd) protein to attenuate a gradient of Wnt/beta-catenin signaling across each segmental anlage. Nkd inhibits Wnt signaling by binding the intracellular protein Dishevelled (Dsh). Mice and humans have two nkd homologs, nkd1 and nkd2, whose encoded proteins can bind Dsh homologs (the Dvl proteins) and inhibit Wnt signaling. To determine whether nkd genes are necessary for murine development, we replaced nkd exons that encode Dvl-binding sequences with IRES-lacZ/neomycin cassettes. Mutants homozygous for each nkd(lacZ) allele are viable with slightly reduced mean litter sizes. Surprisingly, double-knockout mice are viable, with subtle alterations in cranial bone morphology that are reminiscent of mutation in another Wnt/beta-catenin antagonist, axin2. Our data show that nkd function in the mouse is dispensable for embryonic development.

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  • Article: Modulation of wingless signaling by Notch in Drosophila.
    H K Hing, X Sun, S Artavanis-Tsakonas
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    ABSTRACT: Extensive genetic and molecular analyses indicate that Notch acts as a transmembrane receptor in an evolutionarily conserved cell interaction mechanism that appears to control a common step in the progression of an uncommitted cell towards the differentiated state. In Drosophila, Notch mutations were shown to affect the development of a broad spectrum of tissues, including the wing. We found that mutations in the segment polarity gene wingless are capable of acting as dominant enhancers of notchoid, a recessive Notch allele affecting the wing. The Wingless protein is homologous to the mammalian proto-oncoprotein Wnt-1 and is thought to act as the signal in a cell interaction mechanism that specifies differentiation of the embryonic epidermis as well as imaginal structures such as the wing. Although some components of the Wingless signal transduction pathway have been identified, the receptor for Wingless remains elusive. This genetic link between the Wingless and Notch pathways has been further examined by determining the relative expression patterns and subcellular localization of Notch and Wingless in mutant and wild-type backgrounds. We find that Notch is necessary for the implementation of the Wingless signal in specifying normal wing development. We discuss the possibility that Notch is directly involved in the reception of Wingless in the light of current models for the developmental action of Notch.
    Mechanisms of Development 10/1994; 47(3):261-8. · 2.83 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

cranial bone morphology
 
double-knockout mice
 
Dvl proteins
 
embryonic development
 
encode Dvl-binding sequences
 
intracellular protein Dishevelled
 
metazoan animals
 
murine development
 
Mutants homozygous
 
Naked cuticle
 
Nkd
 
nkd exons
 
nkd function
 
nkd genes
 
Nkd inhibits Wnt signaling
 
nkd(lacZ)
 
nkd1
 
nkd2
 
physiological homeostasis
 
Proper embryonic development