Monitoring Notch1 activity in development: Evidence for a feedback regulatory loop

Authors

  • Gonzalo Del Monte,

    1. Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid, Spain
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  • Joaquím Grego-Bessa,

    1. Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid, Spain
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  • Alvaro González-Rajal,

    1. Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid, Spain
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  • Victoria Bolós,

    1. Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid, Spain
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  • José Luis De La Pompa

    Corresponding author
    1. Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid, Spain
    • Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Darwin 3, Campus Cantoblanco, E-28049 Madrid, Spain
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Abstract

Signaling through Notch receptors, which regulate cell fate decisions and embryonic patterning, requires ligand-induced receptor cleavage to generate the signaling active Notch intracellular domain (NICD). Here, we show an analysis at specific developmental stages of the distribution of active mouse Notch1. We use an antibody that recognizes N1ICD, and a highly sensitive staining technique. The earliest N1ICD expression was observed in the mesoderm and developing heart, where we detected expression in nascent endocardium, presumptive cardiac valves, and ventricular and atrial endocardium. During segmentation, N1ICD was restricted to the presomitic mesoderm. N1ICD expression was also evident in arterial endothelium, and in kidney and endodermal derivatives such as pancreas and thymus. Ectodermal N1ICD expression was found in central nervous system and sensory placodes. We found that Notch1 transcription and activity was severely reduced in zebrafish and mouse Notch pathway mutants, suggesting that vertebrate Notch1 expression is regulated by a positive feedback loop. Developmental Dynamics 236:2594–2614, 2007. © 2007 Wiley-Liss, Inc.

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