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Science 332 (6034): 1210-1213

Copyright © 2011 by the American Association for the Advancement of Science

Interaction Between Notch and Hif-α in Development and Survival of Drosophila Blood Cells

Tina Mukherjee,1 William Sang Kim,1 Lolitika Mandal,1,* Utpal Banerjee1,2,{dagger}

Abstract: A blood cell type termed crystal cell in Drosophila functions in clotting and wound healing and requires Notch for specification and maintenance. We report that crystal cells express elevated levels of Sima protein orthologous to mammalian hypoxia-inducible factor–α (Hif-α) even under conditions of normal oxygen availability. In these platelet-like crystal cells, Sima activates full-length Notch receptor signaling via a noncanonical, ligand-independent mechanism that promotes hemocyte survival during both normal hematopoietic development and hypoxic stress. This interaction initiates in early endosomes, is independent of Hif-β (Tango in Drosophila), and does not activate hypoxia response targets. Studies in vertebrate myeloid cells have shown a similar up-regulation of Hif-α protein in well-oxygenated environments. This study provides a mechanistic paradigm for Hif-α/Notch interaction that may be conserved in mammals.

1 Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
2 Molecular Biology Institute, Department of Biological Chemistry, and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA.

* Present address: Indian Institute of Science Education and Research, Mohali, MGSIPAP Complex, Sector 26, Chandigarh 160019, India.

{dagger} To whom correspondence should be addressed. E-mail: banerjee{at}mbi.ucla.edu


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