Lithium-Sensitive Production of Inositol Phosphates During Amphibian Embryonic Mesoderm Induction

Maslanski, John A.; Leshko, LeeAnn; Busa, William B.

doi:10.1126/science.1314424

Cited by 90 publications

(33 citation statements)

References 30 publications

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“…As with Xwnt-8, the primary target in lithium-induced microcephaly has been shown to be the head mesoderm, rather than the neuroctoderm (Hall 1942). Although the molecular mechanism by which the Xwnt-8 signal is transduced is unknown, the effects of lithium in Xenopus are believed to be mediated by an inhibition of the polyphosphoinositide cycle (Busa and Gimlich 1989;Maslanski et al 1992). Our current results strengthen the possibility that some Wnts may utilize a similar signaling pathway.…”

Section: Genes and Developmentsupporting

confidence: 68%

Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus.

Christian¹,

Moon²

1993

Genes Dev.

425

292

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This study analyzes the hierarchy of signals that spatially restrict expression of Xenopus Xwnt-8 to mesodermal cells outside of the Spemann organizer field and examines the potential role that endogenous Xwnt-8 may play in dorsoventral patterning of the embryonic mesoderm. The effects of ectopic introduction of a Nieuwkoop center-like activity or of ectopic expression of goosecoid, on the distribution of endogenous Xwnt-8 transcripts were analyzed. The results of these studies are consistent with the hypothesis that maternally derived signals from the Nieuwkoop center function to positively regulate expression of the homeo box gene goosecoid in Spemann organizer cells, leading to a subsequent repression of Xwnt-8 expression in these cells. This exclusion of Xwnt-8 from cells of the organizer field may be important for normal dorsal development, in that ectopic expression of Xwnt-8 in organizer cells after the midblastula stage, by injection of plasmid DNA, ventralizes the fate of these cells. This is distinct from the previously observed dorsalizing effect of Xwnt-8 when expressed prior to the midblastula stage by injection of RNA. The effects of plasmid-derived Xwnt-8 on isolated blastula animal cap ectoderm were also analyzed. Expression of Xwnt-8 in animal pole ectoderm after the midblastula stage ventralizes the response of dorsal animal pole cells to activin and allows naive ectodermal cells to differentiate as ventral mesoderm in the absence of added growth factors. Collectively, these data are consistent with the hypothesis that Xwnt-8 plays a role in the mesodermal differentiation of ventral marginal zone cells during normal development. Furthermore, endogenous Xwnt-8 may ventralize the response of lateral mesodermal cells to dorsalizing signals from the organizer, thus contributing to the graded nature of the final body pattern.

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Section: Genes and Developmentsupporting

confidence: 68%

Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus.

Christian¹,

Moon²

1993

Genes Dev.

425

292

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“…Tracer Analysis, Enzymatic-Inositol phosphates were dephosphorylated to myoinositol, which was detected using the method of Maslanski et al (51). Briefly, fresh alkaline phosphatase (45 l of 200 units/ml in 0.1 M Tris-HCl, pH 9.0, 0.1 mM ZnCl 2 ) was added to the dry sample and incubated overnight at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Heteromeric, but Not Homomeric, Connexin Channels Are Selectively Permeable to Inositol Phosphates

Ayad

Locke

Koreen

et al. 2006

Journal of Biological Chemistry

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Previous work has shown that channels formed by both connexin (Cx)26 and Cx32 (heteromeric Cx26/Cx32 hemichannels) are selectively permeable to cAMP and cGMP. To further investigate differential connexin channel permeability among second messengers, and the influence of connexin channel composition on the selectivity, the permeability of inositol phosphates with one to four phosphate groups through homomeric Cx26, homomeric Cx32, and heteromeric Cx26/Cx32 channels was examined. Connexin channels were purified from transfected HeLa cells and from rat, mouse, and guinea pig livers, resulting in channels with a broad range of Cx26/ Cx32 aggregate ratios. Permeability to inositol phosphates was assessed by flux through reconstituted channels. Surprisingly, myoinositol and all inositol phosphates tested were permeable through homomeric Cx32 and homomeric Cx26 channels. Even more surprising, heteromeric Cx26/Cx32 channels showed striking differences in permeability among inositol phosphates with three or four phosphate groups and among isomers of inositol triphosphate. Thus, heteromeric channels are selectively permeable among inositol phosphates, whereas the corresponding homomeric channels are not. There was no discernible difference in the permeability of channels with similar Cx26/Cx32 ratios purified from native and heterologous sources. The molecular selectivity of heteromeric channels among three inositol triphosphates could not be accounted for by simple connexin isoform stoichiometry distributions and therefore may depend on specific isoform radial arrangements within the hexameric channels. Dynamic regulation of channel composition in vivo may effectively and efficiently modulate intercellular signaling by inositol phosphates.Connexin channels, which compose most vertebrate gap junctions, mediate direct intercellular movement of ions and molecules. There are ϳ20 isoforms of connexin protein, each forming channels with distinct functional properties. Every known functional deletion of a connexin isoform produces a distinct pathology, and genetic replacement of one connexin (Cx) 2 by another ("knock in") fails to fully compensate (1-3). Pathologies that arise from altered connexin channel function must arise from abnormal molecular movement through connexin channels, whether in magnitude, regulation, or molecular specificity (reviewed in Ref. 4).Gap junction channels form by end-to-end interaction of hemichannels, each consisting of six connexin monomers. Hemichannels are either homomeric (composed of a single connexin isoform) or heteromeric (more than one isoform). Dramatic and surprising degrees of ionic and molecular permselectivity have been observed for homomeric channels (5-13). However, most cells express more than one connexin, and heteromeric connexin channels are common in vivo (14 -18). Heteromeric mixing of different connexin isoforms, producing variation in channel stoichiometry and/or arrangements of isoforms within the hemichannels, may allow cells to dynamically regulate their intercellular co...

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“…PI-PLC-catalyzed hydrolysis of phospholipids to generate second-messenger molecules results from a wide range of stimuli and is implicated in many cellular processes, including mesoderm induction and axis determination in embryonic development (45), phototransduction (7,53,65,66,69,83), secretion (58), growth and differentiation (4,13), muscle contraction (33), and long-term potentiation of synaptic transmission in memory (11). Recent evidence indicates that a PI signaling pathway exists for communication between the nucleus and the cytoplasm (14,54).…”

mentioning

confidence: 99%

A mutation in PLC1, a candidate phosphoinositide-specific phospholipase C gene from Saccharomyces cerevisiae, causes aberrant mitotic chromosome segregation.

Payne¹,

Fitzgerald-Hayes²

1993

Mol. Cell. Biol.

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We identified a putative Saccharomyces cerevisiae homolog of a phosphoinositide-specific phospholipase C (PI-PLC) gene, PLC), which encodes a protein most similar to the 8 class of PI-PLC enzymes. The PLC) gene was isolated during a study of PI-PLC-catalyzed hydrolysis of phospholipids to generate second-messenger molecules results from a wide range of stimuli and is implicated in many cellular processes, including mesoderm induction and axis determination in embryonic development (45), phototransduction (7,53,65,66,69,83), secretion (58), growth and differentiation (4, 13), muscle contraction (33), and long-term potentiation of synaptic transmission in memory (11). Recent evidence indicates that a PI signaling pathway exists for communication between the nucleus and the cytoplasm (14, 54). In addition, PIs are involved in regulating the organization of the cytoskeleton (21,22,55,67). Although many PI-PLC isozymes have been extensively characterized biochemically, the functions of the enzymes within any specific signal transduction pathway have not been elucidated, with the possible exception of the Drosophila PLC-P enzyme, which is known to be involved in phototransduction (7). Recently it was shown that mammalian PLC-11 is regulated by a G-protein-dependent mechanism (72,75,80) and that PLC--yl is regulated by tyrosine phosphorylation (35,47,49,79). It is likely that members of a particular PI-PLC subtype (e.g., 11, ,B2, and 13) are * Corresponding author. t Present address:

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Lithium-Sensitive Production of Inositol Phosphates During Amphibian Embryonic Mesoderm Induction

Cited by 90 publications

References 30 publications

Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus.

Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus.

Heteromeric, but Not Homomeric, Connexin Channels Are Selectively Permeable to Inositol Phosphates

A mutation in PLC1, a candidate phosphoinositide-specific phospholipase C gene from Saccharomyces cerevisiae, causes aberrant mitotic chromosome segregation.

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