Man1, an inner nuclear membrane protein, regulates left–right axis formation by controlling nodal signaling in a node‐independent manner

Ishimura, Akihiko; Chida, Shinsuke; Osada, Shin‐Ichi

doi:10.1002/dvdy.21663

Cited by 17 publications

(9 citation statements)

References 59 publications

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“…2A-C and supplementary material Fig. S2) overlapped with reported Bmp2 (Ishimura et al, 2008;Madabhushi and Lacy, 2011) and Bmp4 (Lawson et al, 1999) expression domains, and intense BMP/Smad activation in a BRElacZ reporter mouse (Monteiro et al, 2004) that monitors BMP/Smad1-5 signaling (Fig. 2F).…”

Section: Formation Of An Ectopic Primitive Streak-like Structure In Ssupporting

confidence: 65%

Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion

et al. 2012

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SUMMARYThe strength and spatiotemporal activity of Nodal signaling is tightly controlled in early implantation mouse embryos, including by autoregulation and feedback loops, and involves secreted and intracellular antagonists. These control mechanisms, which are established at the extra-embryonic/embryonic interfaces, are essential for anterior-posterior patterning of the epiblast and correct positioning of the primitive streak. Formation of an ectopic primitive streak, or streak expansion, has previously been reported in mutants lacking antagonists that target Nodal signaling. Here, we demonstrate that loss-of-function of a major bone morphogenetic protein (BMP) effector, Smad5, results in formation of an ectopic primitive streak-like structure in mutant amnion accompanied by ectopic Nodal expression. This suggests that BMP/Smad5 signaling contributes to negative regulation of Nodal. In cultured cells, we find that BMP-activated Smad5 antagonizes Nodal signaling by interfering with the Nodal-Smad2/4-Foxh1 autoregulatory pathway through the formation of an unusual BMP4-induced Smad complex containing Smad2 and Smad5. Quantitative expression analysis supports that ectopic Nodal expression in the Smad5 mutant amnion is induced by the Nodal autoregulatory loop and a slow positive-feedback loop. The latter involves BMP4 signaling and also induction of ectopic Wnt3. Ectopic activation of these Nodal feedback loops in the Smad5 mutant amnion results in the eventual formation of an ectopic primitive streak-like structure. We conclude that antagonism of Nodal signaling by BMP/Smad5 signaling prevents primitive streak formation in the amnion of normal mouse embryos.

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Section: Formation Of An Ectopic Primitive Streak-like Structure In Ssupporting

confidence: 65%

Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion

et al. 2012

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“…A similar regulation of Nodal expression, independent of node and midline function, was reported in the Man1-deficient mouse, in which TGFβ signaling was disrupted (Ishimura et al, 2008). Taken together, Wnt/β-catenin signaling executes multiple and distinct functions in regulating target organ laterality, which warrant further investigation.…”

Section: Research Articlesupporting

confidence: 60%

Distinct functions of Wnt/β-catenin signaling in KV development and cardiac asymmetry

Lin

2009

Development

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The Wnt/β-catenin pathway exhibits distinct and developmental stage-specific roles during cardiogenesis. However, little is known about the molecular mechanisms of Wnt/β-catenin signaling in the establishment of cardiac left-right (LR) asymmetry. Using zebrafish as an animal model, we show here that Wnt/β-catenin signaling is differentially required in cardiac LR patterning. At an early stage, during asymmetric signal generation, Wnt/β-catenin signaling is necessary for Kupffer's vesicle development and for the regulation of both heart and visceral laterality. At a later stage, during asymmetric signal propagation, excessive Wnt/β-catenin signaling inhibits the transmission of asymmetric cues from the lateral plate mesoderm (LPM) to the cardiac field but not to the developing gut; as such, it only regulates heart laterality. Molecular analysis identifies Gata4 as the downstream target of Wnt/β-catenin signaling in the cardiac field that responds to the Wnt/β-catenin signaling and regulates the competence of the heart field to express left-sided genes. In summary, our results reveal a previously unexpected role of Wnt-Gata4 signaling in the control of asymmetric signal propagation from the LPM to the cardiac field.

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“…These genes are important to maintain optimum growth and development. LEMD3 and LOX are associated with the development of different organs, such as heart ( LEMD3 ), lung and blood vessels ( LOX ) (Maki et al, 2005; Ishimura et al, 2008). The candidate region harboring LEMD3 has also been found to be under selection in Brahman cattle (Ramey et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Signatures of Selection for Environmental Adaptation and Zebu × Taurine Hybrid Fitness in East African Shorthorn Zebu

Bahbahani

Tijjani

Mukasa³

et al. 2017

Front. Genet.

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The East African Shorthorn Zebu (EASZ) cattle are ancient hybrid between Asian zebu × African taurine cattle preferred by local farmers due to their adaptability to the African environment. The genetic controls of these adaptabilities are not clearly understood yet. Here, we genotyped 92 EASZ samples from Kenya (KEASZ) with more than 770,000 SNPs and sequenced the genome of a pool of 10 KEASZ. We observe an even admixed autosomal zebu × taurine genomic structure in the population. A total of 101 and 165 candidate regions of positive selection, based on genome-wide SNP analyses (meta-SS, Rsb, iHS, and ΔAF) and pooled heterozygosity (Hp) full genome sequence analysis, are identified, in which 35 regions are shared between them. A total of 142 functional variants, one novel, have been detected within these regions, in which 30 and 26 were classified as of zebu and African taurine origins, respectively. High density genome-wide SNP analysis of zebu × taurine admixed cattle populations from Uganda and Nigeria show that 25 of these regions are shared between KEASZ and Uganda cattle, and seven regions are shared across the KEASZ, Uganda, and Nigeria cattle. The identification of common candidate regions allows us to fine map 18 regions. These regions intersect with genes and QTL associated with reproduction and environmental stress (e.g., immunity and heat stress) suggesting that the genome of the zebu × taurine admixed cattle has been uniquely selected to maximize hybrid fitness both in terms of reproduction and survivability.

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Man1, an inner nuclear membrane protein, regulates left–right axis formation by controlling nodal signaling in a node‐independent manner

Cited by 17 publications

References 59 publications

Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion

Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion

Distinct functions of Wnt/β-catenin signaling in KV development and cardiac asymmetry

Signatures of Selection for Environmental Adaptation and Zebu × Taurine Hybrid Fitness in East African Shorthorn Zebu

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