Monitoring Notch1 activity in development: evidence for a feedback regulatory loop.
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.
Del Monte
Gonzalo
G
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid, Spain.
Grego-Bessa
Joaquím
J
González-Rajal
Alvaro
A
Bolós
Victoria
V
De La Pompa
José Luis
JL
D000818:Animals; D002319:Cardiovascular System / Q000196:embryology; D019070:Cell Lineage; D002490:Central Nervous System / Q000196:embryology; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D010179:Pancreas / Q000196:embryology; D051881:Receptor, Notch1 / Q000235:genetics* / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism; D013950:Thymus Gland / Q000196:embryology; D014018:Tissue Distribution; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C437805:notch1a protein, zebrafish