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Cell. 2012 Jan 20;148(1-2):273-84. doi: 10.1016/j.cell.2011.10.047.

Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube.

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  • 1Developmental Biology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

Abstract

Secreted signals, known as morphogens, provide the positional information that organizes gene expression and cellular differentiation in many developing tissues. In the vertebrate neural tube, Sonic Hedgehog (Shh) acts as a morphogen to control the pattern of neuronal subtype specification. Using an in vivo reporter of Shh signaling, mouse genetics, and systems modeling, we show that a spatially and temporally changing gradient of Shh signaling is interpreted by the regulatory logic of a downstream transcriptional network. The design of the network, which links three transcription factors to Shh signaling, is responsible for differential spatial and temporal gene expression. In addition, the network renders cells insensitive to fluctuations in signaling and confers hysteresis--memory of the signal. Our findings reveal that morphogen interpretation is an emergent property of the architecture of a transcriptional network that provides robustness and reliability to tissue patterning.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22265416
[PubMed - indexed for MEDLINE]
PMCID:
PMC3267043
Free PMC Article
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