Dataset Information

Lzts2 regulates embryonic cell movements and dorsoventral patterning through interaction with and export of nuclear ?-catenin in zebrafish.

ABSTRACT: Leucine zipper tumor suppressor 2 (Lzts2) functions in the development and progression of various tumors, but its activities in vertebrate embryogenesis remain unclear. Here, we demonstrate that lzts2 transcripts are of maternal origin in zebrafish embryos. Activation of BMP signaling up-regulates zygotic expression of lzts2, whereas canonical Wnt signaling acts upstream of BMP signaling to inhibit lzts2 expression. Abrogation of lzts2 expression by its specific morpholino-enhanced gastrula convergence and extension (CE) movements, dorsalized early embryos, and inhibited specification of midline progenitors for pancreas, liver, and heart. In contrast, ectopic expression of lzts2 led to the delay of CE movements and midline convergence of organ progenitors and resulted in a certain ratio of ventralized embryos. Mechanistically, Lzts2 regulates the migration of embryonic cells and dorsoventral patterning through its limitation of Wnt/?-catenin activity, because it physically interacts with ?-catenin-1 and -2 and transports them out of the nucleus. In addition, both ?-catenin-1 and -2 exhibit redundant functions in activation of Stat3 signaling and in induction of Wnt5/11 expression through inhibition of BMP signaling and stimulation of Cyclops and Squint expression. Thus, Lzts2 regulates gastrula CE movements, dorsoventral patterning, and midline convergence and specification of organ precursors through interaction with and the export of nuclear ?-catenins in zebrafish.

SUBMITTER: Li Y

PROVIDER: S-EPMC3248021 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Lzts2 regulates embryonic cell movements and dorsoventral patterning through interaction with and export of nuclear β-catenin in zebrafish.

Li Yuanyuan Y Li Qing Q Long Yong Y Cui Zongbin Z

The Journal of biological chemistry 20111104 52

Leucine zipper tumor suppressor 2 (Lzts2) functions in the development and progression of various tumors, but its activities in vertebrate embryogenesis remain unclear. Here, we demonstrate that lzts2 transcripts are of maternal origin in zebrafish embryos. Activation of BMP signaling up-regulates zygotic expression of lzts2, whereas canonical Wnt signaling acts upstream of BMP signaling to inhibit lzts2 expression. Abrogation of lzts2 expression by its specific morpholino-enhanced gastrula conv ...[more]

PMID: 22057270

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Project description:Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a high-production volume organophosphate flame retardant widely used within the United States. Within zebrafish, initiation of TDCIPP exposure at 0.75 h post-fertilization (hpf) results in genome-wide alterations in methylation during cleavage (2 hpf) as well as epiboly delay or arrest (at higher concentrations) during late-blastula and early-gastrula (4-6 hpf). To determine whether these TDCIPP-induced effects were associated with impacts on the transcriptome, embryos were exposed to vehicle (0.1% DMSO) or 2 µM TDCIPP from 0.75 hpf to 6 hpf, and total RNA was extracted from triplicate embryo pools per treatment and hybridized onto duplicate Affymetrix Zebrafish Gene 1.0 ST Arrays per RNA sample. Based on transcriptome-wide profiling, TDCIPP resulted in a significant impact on biological processes involved in dorsoventral patterning and bone morphogenetic protein (BMP) signaling. Consistent with these responses, TDCIPP exposure also resulted in strongly dorsalized embryos by 24 hpf-a phenotype that mimicked the effects of dorsomorphin, a potent and selective BMP inhibitor. Moreover, the majority of dorsalized embryos were preceded by epiboly arrest at 6 hpf. Our microarray data also revealed that the expression of sizzled (szl)-a gene encoding a secreted Frizzled-related protein that limits BMP signaling-was significantly decreased by nearly 4-fold at 6 hpf. Therefore, we used a splice-blocking morpholino to test the hypothesis that knockdown of szl phenocopies TDCIPP-induced delays in epiboly progression. Interestingly, contrary to our hypothesis, injection of szl MOs did not affect epiboly progression but, similar to chordin (chd) morphants, resulted in mildly ventralized embryos by 24 hpf. Overall, our findings suggest that TDCIPP-induced epiboly delay may not be driven by decreased szl expression, and that TDCIPP-induced dorsalization may-similar to dorsomorphin-be due to interference with BMP signaling during early zebrafish development.

Dataset Information

Lzts2 regulates embryonic cell movements and dorsoventral patterning through interaction with and export of nuclear ?-catenin in zebrafish.

Publications

Lzts2 regulates embryonic cell movements and dorsoventral patterning through interaction with and export of nuclear β-catenin in zebrafish.

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