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Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo

Cui, Miao and Siriwon, Natnaree and Li, Enhu and Davidson, Eric H. and Peter, Isabelle S. (2014) Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo. Proceedings of the National Academy of Sciences of the United States of America, 111 (47). E5029-E5038. ISSN 0027-8424. PMCID PMC4250154. doi:10.1073/pnas.1419141111.

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Wnt signaling affects cell-fate specification processes throughout embryonic development. Here we take advantage of the well-studied gene regulatory networks (GRNs) that control pregastrular sea urchin embryogenesis to reveal the gene regulatory functions of the entire Wnt-signaling system. Five wnt genes, three frizzled genes, two secreted frizzled-related protein 1 genes, and two Dickkopf genes are expressed in dynamic spatial patterns in the pregastrular embryo of Strongylocentrotus purpuratus. We present a comprehensive analysis of these genes in each embryonic domain. Total functions of the Wnt-signaling system in regulatory gene expression throughout the embryo were studied by use of the Porcupine inhibitor C59, which interferes with zygotic Wnt ligand secretion. Morpholino-mediated knockdown of each expressed Wnt ligand demonstrated that individual Wnt ligands are functionally distinct, despite their partially overlapping spatial expression. They target specific embryonic domains and affect particular regulatory genes. The sum of the effects of blocking expression of individual wnt genes is shown to equal C59 effects. Remarkably, zygotic Wnt-signaling inputs are required for only three general aspects of embryonic specification: the broad activation of endodermal GRNs, the regional specification of the immediately adjacent stripe of ectoderm, and the restriction of the apical neurogenic domain. All Wnt signaling in this pregastrular embryo is short range (and/or autocrine). Furthermore, we show that the transcriptional drivers of wnt genes execute important specification functions in the embryonic domains targeted by the ligands, thus connecting the expression and function of wnt genes by encoded cross-regulatory interactions within the specific regional GRNs.

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Peter, Isabelle S.0000-0003-3685-3147
Additional Information:Copyright © 2014 National Academy of Sciences. Contributed by Eric H. Davidson, October 9, 2014 (sent for review September 12, 2014; reviewed by Robert D. Burke and Randall T. Moon). Published online before print November 10, 2014, doi: 10.1073/pnas.1419141111. We thank Prof. Mike Collins (University of California, Los Angeles) for helpful discussions and for bringing to our attention the small-molecule antagonist C59. This research was supported by National Institutes of Health Grant HD-037105 and the Lucille P. Markey Charitable Trust. This article contains supporting information online at Author contributions: M.C. and I.S.P. designed research; M.C., N.S., and E.L. performed research; M.C., E.H.D., and I.S.P. analyzed data; and M.C., E.H.D., and I.S.P. wrote the paper. Reviewers: R.D.B., University of Victoria; and R.T.M., Howard Hughes Medical Institute, University of Washington. The authors declare no conflict of interest.
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Lucille P. Markey Charitable TrustUNSPECIFIED
Subject Keywords:embryonic interdomain signaling; developmental GRNs; Wnt system regulatory functions; Porcupine
Issue or Number:47
PubMed Central ID:PMC4250154
Record Number:CaltechAUTHORS:20141111-151009684
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Official Citation:Miao Cui, Natnaree Siriwon, Enhu Li, Eric H. Davidson, and Isabelle S. Peter Specific functions of the Wnt signaling system in gene regulatory networks throughout the early sea urchin embryo PNAS 2014 111 (47) E5029-E5038; published ahead of print November 10, 2014, doi:10.1073/pnas.1419141111
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51604
Deposited By: George Porter
Deposited On:11 Nov 2014 23:21
Last Modified:10 Nov 2021 19:13

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