Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Lin, Meng-Ju; Lee, Shyh-Jye

doi:10.1038/srep36188

Cited by 14 publications

(21 citation statements)

References 62 publications

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“…Similar compensatory inconsistency was found in stmn4 mutants, which had a low (< 10%) portion of embryos showing similar phenotype to stmn4 morphants. Interestingly, the authors found that stmn1b was upregulated to compensate in stmn4△5 but not stmn4△4 mutants [56]. In our study, we observed that in response to klf8 deficiency, klf12b , a member of a subgroup of KLF family with a CtBP interaction site, was induced to compensate for the loss of klf8 .…”

Section: Discussionsupporting

confidence: 46%

Klf8 regulates left-right asymmetric patterning through modulation of Kupffer’s vesicle morphogenesis and spaw expression

et al. 2017

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BackgroundAlthough vertebrates are bilaterally symmetric organisms, their internal organs are distributed asymmetrically along a left-right axis. Disruption of left-right axis asymmetric patterning often occurs in human genetic disorders. In zebrafish embryos, Kupffer’s vesicle, like the mouse node, breaks symmetry by inducing asymmetric expression of the Nodal-related gene, spaw, in the left lateral plate mesoderm (LPM). Spaw then stimulates transcription of itself and downstream genes, including lft1, lft2, and pitx2, specifically in the left side of the diencephalon, heart and LPM. This developmental step is essential to establish subsequent asymmetric organ positioning. In this study, we evaluated the role of krüppel-like factor 8 (klf8) in regulating left-right asymmetric patterning in zebrafish embryos.MethodsZebrafish klf8 expression was disrupted by both morpholino antisense oligomer-mediated knockdown and a CRISPR-Cas9 system. Whole-mount in situ hybridization was conducted to evaluate gene expression patterns of Nodal signalling components and the positions of heart and visceral organs. Dorsal forerunner cell number was evaluated in Tg(sox17:gfp) embryos and the length and number of cilia in Kupffer’s vesicle were analyzed by immunocytochemistry using an acetylated tubulin antibody.ResultsHeart jogging, looping and visceral organ positioning were all defective in zebrafish klf8 morphants. At the 18–22 s stages, klf8 morphants showed reduced expression of genes encoding Nodal signalling components (spaw, lft1, lft2, and pitx2) in the left LPM, diencephalon, and heart. Co-injection of klf8 mRNA with klf8 morpholino partially rescued spaw expression. Furthermore, klf8 but not klf8△zf overexpressing embryos showed dysregulated bilateral expression of Nodal signalling components at late somite stages. At the 10s stage, klf8 morphants exhibited reductions in length and number of cilia in Kupffer’s vesicle, while at 75% epiboly, fewer dorsal forerunner cells were observed. Interestingly, klf8 mutant embryos, generated by a CRISPR-Cas9 system, showed bilateral spaw expression in the LPM at late somite stages. This observation may be partly attributed to compensatory upregulation of klf12b, because klf12b knockdown reduced the percentage of klf8 mutants exhibiting bilateral spaw expression.ConclusionsOur results demonstrate that zebrafish Klf8 regulates left-right asymmetric patterning by modulating both Kupffer’s vesicle morphogenesis and spaw expression in the left LPM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-017-0351-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 46%

Klf8 regulates left-right asymmetric patterning through modulation of Kupffer’s vesicle morphogenesis and spaw expression

et al. 2017

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“…Among them, 9 genes including Stmn4 , L1cam , Tenm4 , Clca3b , Gzme , Mmp10 , Igfbp2 , Creb5 and Slc14a1 were significantly down-regulated in WT cells but significantly up-regulated in PPARγ/+ cells from 0d to 5d. In zebrafish study, the functional analysis of stathmin-like 4 ( Stmn4 ) had shown its essential roles in the maintenance of neural progenitor cells, whose expression was revealed to be enriched in the diencephalon in situ hybridization analysis 18 , 19 . STMN4 gene has been also reported to be involved in neuroblastoma cell differentiation 20 .…”

Section: Resultsmentioning

confidence: 99%

A transcriptomic study of myogenic differentiation under the overexpression of PPARγ by RNA-Seq

et al. 2017

Sci Rep

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To study the cellular and molecular function of peroxisome proliferator-activated receptor γ (PPARγ) in skeletal muscle differentiation, we have generated inducible gain-of-function to overexpress PPARγ in C2C12 myoblasts. In order to identify PPARγ targets, RNA sequencing (RNA-seq) was used to evaluate and quantify the transcriptomes and expression patterns during myogenic differentiation under the overexpression of PPARγ. The formation of myotubes and the expression of muscle-specific myogenic genes such as MyoD and MyoG may be inhibited by PPARγ overexpression. Multiple genes and pathways were significantly involved in this process, including 11 genes such as Fndc9 and Slc14a1 with fundamental change of regulation modes, 9 genes of which were validated by the data of qRT-PCR. Our studies demonstrate that PPARγ would play critical roles on myoblasts differentiation, mediating crosstalk among several pathways and transcription factors. Our data is available in the Gene Expression Omnibus (GEO) database with the accession number as GSE99399.

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“…Wnt1 has recently been proposed to mediate the timing of neurogenesis in the midbrain by driving Fgf8 expression at the boundary and gradually suppressing it away from the boundary by inducing Sprouty expression so that Fgf dependent her5 also recedes (Dyer et al, 2014 ). Wnt1 may also function to promote neural stem cell identity in the dorsal midbrain and MHB (Miyake et al, 2012 ; Lin and Lee, 2016 ), possibly regulated by Fgf3/8-dependent Fgf22 signaling (Miyake and Itoh, 2013 ) and may contribute to shaping the MH by regulating the cytoskeleton during axon guidance (Ciani and Salinas, 2005 ). In the hindbrain, differentiation of unique tegmentum nuclei identities happens in spatiotemporal waves emanating from the upper rhombic lip.…”

Section: Midbrain Hindbrain Domain Morphogenesis and Patterningmentioning

confidence: 99%

“…However, both Wnt and Fgf signaling can inhibit GSK3, the primary component of the destruction complex that modulates beta-catenin levels (Dailey et al, 2005 ). Thus, a careful balance of Wnt/Fgf signaling may affect Wnt target genes during MH development such as snail (Yook et al, 2005 ) and twist (Klymkowsky et al, 2010 ), zic2a/5 (Nyholm et al, 2009 ), cyclinD (Megason and McMahon, 2002 ), stmn4 (Lin and Lee, 2016 ), and dpagt1 (Varelas et al, 2014 ), genes known to affect cell proliferation, dorsolateral hinge-point (DLHP) formation, and adhesion. Classical Fgf signaling may also be important in Bergman glial fate specification in the cerebellum (Meier et al, 2014 ).…”

Section: Morphogenetic Roles For Wnt and Fgf Signaling During Constrimentioning

confidence: 99%

Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling

et al. 2017

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A constriction in the neural tube at the junction of the midbrain and hindbrain is a conserved feature of vertebrate embryos. The constriction is a defining feature of the midbrain-hindbrain boundary (MHB), a signaling center that patterns the adjacent midbrain and rostral hindbrain and forms at the junction of two gene expression domains in the early neural plate: an anterior otx2/wnt1 positive domain and a posterior gbx/fgf8 positive domain. otx2 and gbx genes encode mutually repressive transcription factors that create a lineage restriction boundary at their expression interface. Wnt and Fgf genes form a mutually dependent feedback system that maintains their expression domains on the otx2 or gbx side of the boundary, respectively. Constriction morphogenesis occurs after these conserved gene expression domains are established and while their mutual interactions maintain their expression pattern; consequently, mutant studies in zebrafish have led to the suggestion that constriction morphogenesis should be considered a unique phase of MHB development. We analyzed MHB morphogenesis in fgf8 loss of function zebrafish embryos using a reporter driven by the conserved wnt1 enhancer to visualize anterior boundary cells. We found that fgf8 loss of function results in a re-activation of wnt1 reporter expression posterior to the boundary simultaneous with an inactivation of the wnt1 reporter in the anterior boundary cells, and that these events correlate with relaxation of the boundary constriction. In consideration of other results that correlate the boundary constriction with Wnt and Fgf expression, we propose that the maintenance of an active Wnt-Fgf feedback loop is a key factor in driving the morphogenesis of the MHB constriction.

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Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae

Cited by 14 publications

References 62 publications

Klf8 regulates left-right asymmetric patterning through modulation of Kupffer’s vesicle morphogenesis and spaw expression

Klf8 regulates left-right asymmetric patterning through modulation of Kupffer’s vesicle morphogenesis and spaw expression

A transcriptomic study of myogenic differentiation under the overexpression of PPARγ by RNA-Seq

Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling

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