Kim, YT and Joshi, SD and Messner, WC and LeDuc, PR and Davidson, LA
(2011)
Detection of dynamic spatiotemporal response to periodic chemical stimulation in a Xenopus embryonic tissue.
PLoS ONE, 6 (1).
Abstract
Embryonic development is guided by a complex and integrated set of stimuli that results in collective system-wide organization that is both time and space regulated. These regulatory interactions result in the emergence of highly functional units, which are correlated to frequency-modulated stimulation profiles. We have determined the dynamic response of vertebrate embryonic tissues to highly controlled, time-varying localized chemical stimulation using a microfluidic system with feedback control. Our approach has enabled localized spatiotemporal manipulation of the steroid hormone dexamethasone (DEX) in Animal Cap (AC) tissues isolated from gastrulating Xenopus embryos. Using this approach we investigated cell-scale responses to precisely controlled stimulation by tracking the redistribution of a GFP-tagged DEXreporter constructed from the human glucocorticoid receptor (GR). We exposed defined regions of a single AC explant to different stimulation conditions-continuous stimulation, periodic stimulation, and no stimulation. We observed collective behavior of the GR transport into the nucleus was first-order. Furthermore, the dynamic response was well-modeled by a first-order differential equation with a single time derivative. The model predicted that responses to periodic stimulations closely matched the results of the frequency-based experiments. We find that stimulation with localized bursts versus continuous stimulation can result in highly distinct responses. This finding is critical as controlled space and time exposure to growth factors is a hallmark of complex processes in embryonic development. These complex responses to cellular signaling and transport machinery were similar to emergent behaviors in other complex systems, suggesting that even within a complex embryonic tissue, the overall system can converge toward a predictive first-order response. © 2011 Kim et al.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
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| Date: |
9 February 2011 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
6 |
| Number: |
1 |
| DOI or Unique Handle: |
10.1371/journal.pone.0014624 |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Refereed: |
Yes |
| MeSH Headings: |
Animals; Biological Transport; Dexamethasone--pharmacology; Embryo, Nonmammalian--cytology; Embryo, Nonmammalian--drug effects; Embryonic Development--drug effects; Embryonic Development--physiology; Green Fluorescent Proteins--diagnostic use; Humans; Microfluidic Analytical Techniques; Receptors, Glucocorticoid--metabolism; Signal Transduction; Stimulation, Chemical; Time Factors; Tissue Distribution; Xenopus |
| Other ID: |
NLM PMC3031512 |
| PubMed Central ID: |
PMC3031512 |
| PubMed ID: |
21305055 |
| Date Deposited: |
03 Aug 2012 18:50 |
| Last Modified: |
25 Jan 2019 21:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13356 |
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