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Encoding of temporal signals by the TGF-β Pathway and implications for embryonic patterning

Cornell Affiliated Author(s)

Author

B. Sorre
A. Warmflash
A.H. Brivanlou
E. Siggia

Abstract

Genetics and biochemistry have defined the components and wiring of the signaling pathways that pattern the embryo. Among them, the transforming growth factor β (TGF-β) pathway has the potential to behave as a morphogen: invitro experiments established that it can dictate cell fate in a concentration-dependent manner. How morphogens convey positional information in a developing embryo, when signal levels change with time, is less understood. Using integrated microfluidic cell culture and time-lapse microscopy, we demonstrate here that the speed of ligand presentation has a key and previously unexpected influence on TGF-β signaling outcomes. The response to a TGF-β concentration step is transient and adaptive: slowly increasing the ligand concentration diminishes the response, and well-spaced pulses of ligand combine additively, resulting in greater pathway output than with constant stimulation. Our results suggest that in an embryonic context, the speed of change of ligand concentration is an instructive signal for patterning. © 2014 Elsevier Inc.

Date Published

Journal

Developmental Cell

Volume

30

Issue

3

Number of Pages

334-342,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905752998&doi=10.1016%2fj.devcel.2014.05.022&partnerID=40&md5=5947fd7a7f4bfd1f36b2e77030c0c34f

DOI

10.1016/j.devcel.2014.05.022

Research Area

Funding Source

PHY-0954398
R01 HD32105
R01GM101653
ALTF 1476-2010

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