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Proc Natl Acad Sci U S A. 2017 May 23;114(21):5467-5472. doi: 10.1073/pnas.1703205114. Epub 2017 May 10.

Development of an optimized synthetic Notch receptor as an in vivo cell-cell contact sensor.

Author information

1
Department of Genetics, Harvard Medical School, Boston, MA 02115.
2
School of Life Science and Technology, Tongji University, Shanghai 200092, China.
3
Department of Genetics, Harvard Medical School, Boston, MA 02115; perrimon@genetics.med.harvard.edu.
4
Howard Hughes Medical Institute, Boston, MA 02115.

Abstract

Detection and manipulation of direct cell-cell contact in complex tissues is a fundamental and challenging problem in many biological studies. Here, we report an optimized Notch-based synthetic receptor (synNQ) useful to study direct cell-cell interactions in Drosophila With the synNQ system, cells expressing a synthetic receptor, which contains Notch activation machinery and a downstream transcriptional activator, QF, are activated by a synthetic GFP ligand expressed by contacting neighbor cells. To avoid cis-inhibition, mutually exclusive expression of the synthetic ligand and receptor is achieved using the "flippase-out" system. Expression of the synthetic GFP ligand is controlled by the Gal4/UAS system for easy and broad applications. Using synNQ, we successfully visualized cell-cell interactions within and between most fly tissues, revealing previously undocumented cell-cell contacts. Importantly, in addition to detection of cells in contact with one another, synNQ allows for genetic manipulation in all cells in contact with a targeted cell population, which we demonstrate in the context of cell competition in developing wing disks. Altogether, the synNQ genetic system will enable a broad range of studies of cell contact in developmental biology.

KEYWORDS:

Drosophila; Notch; cell–cell contact; sensor

PMID:
28490499
PMCID:
PMC5448223
DOI:
10.1073/pnas.1703205114
[Indexed for MEDLINE]
Free PMC Article

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