Xenopus nodal related-1 is indispensable only for left-right axis determination

Toyoizumi, Ryuji; Ogasawara, Tsuyoshi; Takeuchi, Shigeo; Mogi, Kazue

doi:10.1387/ijdb.052008rt

Cited by 26 publications

(36 citation statements)

References 95 publications

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“…To determine whether the tubulin-regulated events function in the same pathway as known early LR mechanisms and control downstream asymmetric transcription, we asked whether the expression of tubulin mutants perturbed the normally left-sided expression of the earliest known asymmetric gene in Xenopus: the TGF-β signaling factor Nodal (Xnr-1) (22). Xnr-1 is normally expressed only on the left side of the embryo at approximately stage 22 (23).…”

Section: Resultsmentioning

confidence: 99%

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Lobikin

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

104

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Many types of embryos' bodyplans exhibit consistently oriented laterality of the heart, viscera, and brain. Errors of left-right patterning present an important class of human birth defects, and considerable controversy exists about the nature and evolutionary conservation of the molecular mechanisms that allow embryos to reliably orient the left-right axis. Here we show that the same mutations in the cytoskeletal protein tubulin that alter asymmetry in plants also affect very early steps of left-right patterning in nematode and frog embryos, as well as chirality of human cells in culture. In the frog embryo, tubulin α and tubulin γ-associated proteins are required for the differential distribution of maternal proteins to the left or right blastomere at the first cell division. Our data reveal a remarkable molecular conservation of mechanisms initiating left-right asymmetry. The origin of laterality is cytoplasmic, ancient, and highly conserved across kingdoms, a fundamental feature of the cytoskeleton that underlies chirality in cells and multicellular organisms.C. elegans | Xenopus | symmetry breaking C onsistent laterality is a fascinating aspect of embryonic development and has considerable implications for the physiology and behavior of the organism. Although vertebrates are generally bilaterally symmetric externally, most internal organs, such as the heart, viscera, and brain display asymmetric structure and/or unilateral positioning with respect to the left-right (LR) axis. A common defect in LR patterning is the loss of concordance among the sidedness of individual organs known as heterotaxia. In human beings, abnormalities in the proper development of laterality occur in more than 1 in 8,000 live births and often have significant medical consequences (1). Organ asymmetry is highly conserved among species; however, considerable controversy exists about the early steps of LR patterning among phyla (2-4) and the physical mechanisms that can break symmetry (5).One model predicts that cilia-driven extracellular fluid flow during gastrulation is the origin of LR asymmetry (6). Because numerous species initiate asymmetry before (or without) the presence of cilia (7,8), this model implies that asymmetry generation must be poorly conserved, with numerous distinct mechanisms used throughout phyla. However, "ciliary" proteins, such as left-right dynein, known to be important for LR patterning, also have intracellular roles compatible with cilia-independent functions in laterality (9-12). In contrast to the nodal flow model, we have suggested that asymmetry is instead an ancient, well-conserved property of individual cells arising from the chirality of cytoskeletal structures that is subsequently amplified by physiological mechanisms (4,12,13). Thus, we sought the most evolutionarily distant model systems, and ones that are known not to rely on cilia for LR patterning, to test the hypothesis of fundamental molecular conservation of asymmetry mechanisms.Recent findings in Arabidopsis thaliana have shown that mutatio...

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Section: Resultsmentioning

confidence: 99%

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Lobikin

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

104

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“…The mechanism of determination of left-right asymmetry in vertebrates, various signals from the right and left sides of the node or its equivalent area to the anterior part of the embryo appears to involve induction of the expression of Nodal on the left side with concomitant suppression of Nodal expression on the right side (Levin et al, 1995;Collignon et al, 1996;Lowe et al, 1996;Lohr et al, 1997). This is followed by the restricted expression of transcription factors, such as Pitx2 on only the left side of the embryo (Campione et al, 1999;Patel et al, 1999;Campione et al, 2001;Yu et al, 2001;Mogi et al, 2003;Toyoizumi et al, 2005), BMP on the right side alone (Ramsdell et al, 1999;Branford et al, 2000;Monsoro-Burq and Le Douarin, 2000;Monsoro-Burq and Le Douarin, 2001) and SnR (Issac et al, 1997;Patel et al, 1999). It has been suggested that these factors are also important in determining the rightward direction of hearttube looping in mammalian, avian and amphibian embryos.…”

Section: Discussionmentioning

confidence: 99%

“…Of these genes, Nodal, which is expressed only in the left side of the embryo, is important in determining embryonic leftright asymmetry across many species (Levin et al, 1995;Collignon et al, 1996;Lowe et al, 1996;Lohr et al, 1997;Patel et al, 1999;Mogi et al, 2003;Toyoizumi et al, 2005). Therefore, in the present study, we additionally analyzed the relationship between the heart-tube loop direction in right-and left-half embryos and the expression of CyNodal, a nodal-related gene of newt (Ito et al, 2006), therein.…”

Section: Introductionmentioning

confidence: 97%

“…Recent studies have also implicated asymmetrically expressed genes in the determination of embryonic left-right asymmetry, including Nodal (Levin et al, 1995;Collignon et al, 1996;Lowe et al, 1996;Lohr et al, 1997;Patel et al, 1999;Mogi et al, 2003;Toyoizumi et al, 2005), Pitx2 (Campione et al, 1999;Patel et al, 1999;Campione et al, 2001;Yu et al, 2001;Mogi et al, 2003;Toyoizumi et al, 2005), BMP (Ramsdell and Yost, 1999;Branford et al, 2000;Monsoro-Burq and Le Douarin, 2000;Monsoro-Burq and Le Douarin, 2001) and SnR (Issac et al, 1997, Patel et al, 1999. Of these genes, Nodal, which is expressed only in the left side of the embryo, is important in determining embryonic leftright asymmetry across many species (Levin et al, 1995;Collignon et al, 1996;Lowe et al, 1996;Lohr et al, 1997;Patel et al, 1999;Mogi et al, 2003;Toyoizumi et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heart formation and left-right asymmetry in separated right and left embryos of a newt

Takano

Ito²,

Obata³

et al. 2007

Int. J. Dev. Biol.

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During vertebrate cardiac development, the heart tube formed by fusion of right and left presumptive cardiac mesoderms (PCMs) undergoes looping toward the right, resulting in an asymmetrical heart. Here, we examined the right and left PCMs with regard to heart-tube looping using right-and left-half newt embryos (Cynops pyrrhogaster ). In the half embryos, the rightward (normal) loop of the heart tube was formed from the left PCM, irrespective of the timing of its separation, while the leftward (reversed) loop of the heart tube was formed from the right PCM, separated by stage 18. In addition, the direction of the leftward loop was inverted to the rightward direction in right-half embryos bisected after stage 18. Incision or resection of the embryonic caudal region implicated interactions between the right and left sides of this region as crucial for inverting the direction of the heart-tube loop from leftward to rightward in the right-half embryos. In situ hybridization of CyNodal (Cynops nodal-related gene) suggested that the inversion of heart looping in the right-half embryos has no association with the CyNodal expression pattern. Based on these findings, we propose a mechanism for the rightward looping underlying normal amphibian cardiac development.

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“…Injection of increasing amounts of MOs directed against activin caused first the downregulation of goosecoid expression and only later the down-regulation of Xbra (Piepenburg et al 2004), arguing that a higher concentration of activin is required for expression of goosecoid than is required for Xbra. Knockdown of individual nodal-related proteins has little effect on the early specification of mesoderm (Toyoizumi et al 2005), but it is possible to use "Cerberus-short," a truncated version of the secreted inhibitory molecule Cerberus (Bouwmeester et al 1996), to inhibit the activities of all the nodal-related proteins, and experiments of this sort show that the nodal-related proteins are most active in dorsal regions of the embryo and least active ventrally (Agius et al 2000). Finally, experiments making use of antibodies directed against an activated form of Smad2, a component of the activin/ nodal signal transduction pathway, reveal that levels of TGF-b signaling are higher on the dorsal side of the embryo than on the ventral (Faure et al 2000;Schohl and Fagotto 2002).…”

Section: Evidence For Graded Signaling: In Vivomentioning

confidence: 99%

Forming and Interpreting Gradients in the Early Xenopus Embryo

Smith

2009

Cold Spring Harbor Perspectives in Biology

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The amphibian embryo provides a powerful model system to study morphogen gradients because of the ease with which it is possible to manipulate the early embryo. In particular, it is possible to introduce exogenous sources of morphogen, to follow the progression of the signal, to monitor the cellular response to induction, and to up-or down-regulate molecules that are involved in all aspects of long-range signaling. In this article, I discuss the evidence that gradients exist in the early amphibian embryo, the way in which morphogens might traverse a field of cells, and the way in which different concentrations of morphogens might be interpreted to activate the expression of different genes.

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Xenopus nodal related-1 is indispensable only for left-right axis determination

Cited by 26 publications

References 95 publications

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Early, nonciliary role for microtubule proteins in left–right patterning is conserved across kingdoms

Heart formation and left-right asymmetry in separated right and left embryos of a newt

Forming and Interpreting Gradients in the Early Xenopus Embryo

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