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Znf76 is associated with development of the eyes, midbrain, MHB, and hindbrain in zebrafish embryos.

ABSTRACT: ZNF76 is a transcriptional repressor that targets the TATA-binding protein (TBP) and plays an essential role during brain development; however, its function during embryogenesis remains unclear. Here, we report the expression pattern and potential functions of znf76 in zebrafish embryos. Maternal transcripts of znf76 were detected at low levels in embryos at the 1-cell stage, with zygotic transcripts appearing at the sphere stage. At the bud stage, the distribution of znf76 transcripts was polarized to the anterior and posterior regions of the embryos, and znf76 transcripts were further restricted to the trigeminal placode and proctodeum posterior gut of the embryos at 18?h postfertilization (hpf). znf76 transcripts were localized to the midbrain-hindbrain boundary (MHB), hindbrain, and developing eyes at 24 hpf. Ectopic expression of znf76 with 5'-capped znf76 mRNA microinjected into embryos at the 1-cell stage caused phenotypic defects in the eyes, MHB, hindbrain, and spinal cord. Overexpression of znf76 resulted in a drastic reduction of pax2a, fgf8a, and rx1 transcripts in the optic stalk, MHB, and eyes, respectively. Taken together, these data indicate that Znf76 governs developmental processes in the MHB, hindbrain, and eyes in zebrafish embryos. We also discuss the Fgf8 signaling networks associated with the Znf76 function.

SUBMITTER: Jung J

PROVIDER: S-EPMC6394295 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Znf76 is associated with development of the eyes, midbrain, MHB, and hindbrain in zebrafish embryos.

Jung Jangham J Udhaya Kumar S S Choi Issac I Huh Tea-Lin TL Rhee Myungchull M

Animal cells and systems 20190222 1

ZNF76 is a transcriptional repressor that targets the TATA-binding protein (TBP) and plays an essential role during brain development; however, its function during embryogenesis remains unclear. Here, we report the expression pattern and potential functions of znf76 in zebrafish embryos. Maternal transcripts of znf76 were detected at low levels in embryos at the 1-cell stage, with zygotic transcripts appearing at the sphere stage. At the bud stage, the distribution of znf76 ...[more]

PMID: 30834156

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Project description:BackgroundStudies in mouse, Xenopus and chicken have shown that Otx2 and Gbx2 expression domains are fundamental for positioning the midbrain-hindbrain boundary (MHB) organizer. Of the two zebrafish gbx genes, gbx1 is a likely candidate to participate in this event because its early expression is similar to that reported for Gbx2 in other species. Zebrafish gbx2, on the other hand, acts relatively late at the MHB. To investigate the function of zebrafish gbx1 within the early neural plate, we used a combination of gain- and loss-of-function experiments.ResultsWe found that ectopic gbx1 expression in the anterior neural plate reduces forebrain and midbrain, represses otx2 expression and repositions the MHB to a more anterior position at the new gbx1/otx2 border. In the case of gbx1 loss-of-function, the initially robust otx2 domain shifts slightly posterior at a given stage (70% epiboly), as does MHB marker expression. We further found that ectopic juxtaposition of otx2 and gbx1 leads to ectopic activation of MHB markers fgf8, pax2.1 and eng2. This indicates that, in zebrafish, an interaction between otx2 and gbx1 determines the site of MHB development. Our work also highlights a novel requirement for gbx1 in hindbrain development. Using cell-tracing experiments, gbx1 was found to cell-autonomously transform anterior neural tissue into posterior. Previous studies have shown that gbx1 is a target of Wnt8 graded activity in the early neural plate. Consistent with this, we show that gbx1 can partially restore hindbrain patterning in cases of Wnt8 loss-of-function. We propose that in addition to its role at the MHB, gbx1 acts at the transcriptional level to mediate Wnt8 posteriorizing signals that pattern the developing hindbrain.ConclusionOur results provide evidence that zebrafish gbx1 is involved in positioning the MHB in the early neural plate by refining the otx2 expression domain. In addition to its role in MHB formation, we have shown that gbx1 is a novel mediator of Wnt8 signaling during hindbrain patterning.

Dataset Information

Znf76 is associated with development of the eyes, midbrain, MHB, and hindbrain in zebrafish embryos.

Publications

Znf76 is associated with development of the eyes, midbrain, MHB, and hindbrain in zebrafish embryos.

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