Combined Automated Annotation using Multiple IEA Methods
A regulatory gene network that directs micromere specification in the sea urchin embryo.
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pmar1 encodes a paired-class homeodomain factor expressed only in micromeres during cleavage/early blastula, activated by Otx and beta-catenin/Tcf, and acting as a repressor of a repressor.
"pmar1 is expressed only during cleavage and early blastula stages, and exclusively in micromeres. It is initially activated as soon as the micromeres are formed, in response to Otx and beta-Catenin/Tcf inputs."
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Pmar1 mRNA and an Engrailed-Pmar1 fusion give identical derepression phenotypes, establishing that Pmar1 is a repressor.
"In both cases, the effects are derepression: of the delta gene; and of skeletogenic genes, including several transcription factors normally expressed only in micromere descendants, and also a set of downstream skeletogenic differentiation genes."
Activation of pmar1 controls specification of micromeres in the sea urchin embryo.
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Pmar1 expression rescues all micromere functions in beta-catenin-blocked micromeres transplanted into micromereless hosts.
"When such beta-catenin-blocked micromeres also express Pmar1, all observed micromere functions are rescued."
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Mosaic Pmar1 expression induces ectopic endo16 in adjacent cells, showing Pmar1 controls the early endomesoderm induction signal.
"Pmar1 expressed mosaically from inserted DNA constructs causes induction of ectopic Endo 16 in adjacent cells"
A missing link in the sea urchin embryo gene regulatory network: hesC and the double-negative specification of micromeres.
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hesC is the repressor-of-micromeres gene repressed by Pmar1; hesC knockdown phenocopies global pmar1 overexpression.
"As logically required, blockade of hesC mRNA translation and global overexpression of pmar1 mRNA have the same effect, which is to cause all of the cells of the embryo to express micromere-specific genes."
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Direct Pmar1 binding to hesC regulatory DNA is inferred but not yet demonstrated.
"Although this remains to be finally authenticated by identification of the cis -regulatory target sites, HesC interactions with the target genes of Fig. 1 D are likely to be direct, as is likely to be the interaction of Pmar1 with the hesC regulatory apparatus."
Global regulatory logic for specification of an embryonic cell lineage.
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pmar1 is a small cluster of near-identical genes activated by beta-catenin/Tcf plus Otx, expressed transiently from late fourth cleavage.
"The first genes in the sequence are the pmar1 genes (there is a cluster of several very similar pmar1 genes). The pmar1 genes are activated by the β-catenin/Tcf transcription complex plus Otx"
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pmar1 is necessary and sufficient for skeletogenic micromere specification.
"So pmar1 is necessary and sufficient; no other β-catenin/Tcf target need be involved."
R11: a cis-regulatory node of the sea urchin embryo gene network that controls early expression of SpDelta in micromeres.
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The delta R11 cis-regulatory element responds to the pmar1 repression system as predicted; this is an indirect (via HesC) readout of Pmar1 function.
"this cis-regulatory element is able to drive the expression of a reporter gene in the same cells and at the same time that the endogenous delta gene is expressed, and that temporally, spatially, and quantitatively it responds to the pmar1 repression system"
Activation of the skeletogenic gene regulatory network in the early sea urchin embryo.
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alx1 and delta are activated before hesC is downregulated, implying additional pmar1-controlled repressors beyond hesC.
"We postulate the existence of additional, unidentified repressors that are controlled by pmar1, and propose that the ability of pmar1 to derepress alx1 and delta is regulated by the unequal division of vegetal blastomeres."
pmar1/phb homeobox genes and the evolution of the double-negative gate for endomesoderm specification in echinoderms.
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The Pmar1-hesC linkage is a euechinoid innovation; cidaroid Pmar1 and starfish Phb promote endomesoderm specification via an unknown repressor that is not HesC.
"we have identified the basal echinoid (cidaroid) pmar1 gene, which also promotes endomesoderm specification but not by repressing hesC"