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Gene regulatory network subcircuit controlling a dynamic spatial pattern of signaling in the sea urchin embryo

Smith, Joel and Davidson, Eric H. (2008) Gene regulatory network subcircuit controlling a dynamic spatial pattern of signaling in the sea urchin embryo. Proceedings of the National Academy of Sciences of the United States of America, 105 (51). pp. 20089-20094. ISSN 0027-8424. PMCID PMC2629318. doi:10.1073/pnas.0806442105.

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We dissect the transcriptional regulatory relationships coordinating the dynamic expression patterns of two signaling genes, wnt8 and delta, which are central to specification of the sea urchin embryo endomesoderm. cis-Regulatory analysis shows that transcription of the gene encoding the Notch ligand Delta is activated by the widely expressed Runx transcription factor, but spatially restricted by HesC-mediated repression through a site in the delta 5′UTR. Spatial transcription of the hesC gene, however, is controlled by Blimp1 repression. Blimp1 thus represses the repressor of delta, thereby permitting its transcription. The blimp1 gene is itself linked into a feedback circuit that includes the wnt8 signaling ligand gene, and we showed earlier that this circuit generates an expanding torus of blimp1 and wnt8 expression. The finding that delta expression is also controlled at the cis-regulatory level by the blimp1-wnt8 torus-generating subcircuit now explains the progression of Notch signaling from the mesoderm to the endoderm of the developing embryo. Thus the specific cis-regulatory linkages of the gene regulatory network encode the coordinated spatial expression of Wnt and Notch signaling as they sweep outward across the vegetal plate of the embryo.

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Additional Information:© 2008 by The National Academy of Sciences of the USA. Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX and approved August 28, 2008 (received for review July 7, 2008). This article is a PNAS Direct Submission. Published online before print December 22, 2008, doi: 10.1073/pnas.0806442105 We are grateful to Roger Revilla-i-Domingo for whole-mount in situ hybridizations, Christina Theodoris for high-resolution expression time-course measurements, and Julie Hahn for construction of BAC recombinants. J.S. is a Fellow of the California Institute for Regenerative Medicine (CIRM). Research was supported by National Institute of Child Health and Human Development Grant HD-037105 and National Institute of General Medical Sciences Grants GM-075089 and GM-061005. This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Gene Networks in Animal Development and Evolution,” held February 15–16, 2008, at the Arnold and Mabel Beckman Center of the National Academies of Sciences and Engineering in Irvine, CA. The complete program and audio files of most presentations are available on the NAS web site at Author contributions: J.S. and E.H.D. designed research; J.S. performed research; J.S. and E.H.D. analyzed data; and J.S. and E.H.D. wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at
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California Institute for Regenerative Medicine (CIRM)UNSPECIFIED
Subject Keywords:Blimp1; Delta; HesC; Notch; Wnt
Issue or Number:51
PubMed Central ID:PMC2629318
Record Number:CaltechAUTHORS:SMIpnas08
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13015
Deposited By: Archive Administrator
Deposited On:15 Jan 2009 18:01
Last Modified:08 Nov 2021 22:34

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