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Salient features of the ciliated organ of asymmetry.

Amack JD - Bioarchitecture (2014)

Bottom Line: These 'LR cilia' are found in the ventral node and posterior notochordal plate in mammals, the gastrocoel roof plate in amphibians and Kupffer's vesicle in teleost fish.I consider these transient ciliated structures as the 'organ of asymmetry' that directs LR patterning of the developing embryo.Variations in size and morphology of the organ of asymmetry in different vertebrate species have raised questions regarding the fundamental features that are required for LR determination.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology; State University of New York; Upstate Medical University; Syracuse, NY USA.

ABSTRACT
Many internal organs develop distinct left and right sides that are essential for their functions. In several vertebrate embryos, motile cilia generate an asymmetric fluid flow that plays an important role in establishing left-right (LR) signaling cascades. These 'LR cilia' are found in the ventral node and posterior notochordal plate in mammals, the gastrocoel roof plate in amphibians and Kupffer's vesicle in teleost fish. I consider these transient ciliated structures as the 'organ of asymmetry' that directs LR patterning of the developing embryo. Variations in size and morphology of the organ of asymmetry in different vertebrate species have raised questions regarding the fundamental features that are required for LR determination. Here, I review current models for how LR asymmetry is established in vertebrates, discuss the cellular architecture of the ciliated organ of asymmetry and then propose key features of this organ that are critical for orienting the LR body axis.

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Figure 1. Working model for how LR asymmetry is established in vertebrate embryos. (A) Asymmetric Nodal signaling guides asymmetric organ development. The TGFβ signaling molecule Nodal initiates its own expression in left lateral plate mesoderm (LPM) to expand asymmetric patterning along the left side of the embryo and induces expression of Lefty and Pitx2. Lefty molecules function as Nodal antagonists in the embryonic midline (dashed line) and LPM to place boundaries on Nodal signaling. Pitx2 is a transcription factor thought to control genes involved in asymmetric morphogenesis of visceral organs. (B) Asymmetric fluid flow in the ciliated organ of asymmetry is translated into asymmetric Nodal signaling. Motile LR cilia (red) generate a leftward flow that results in increased Ca2+ signals on the left side of the organ of asymmetry and elevated expression of Cerebrus/Dan family Nodal antagonists (Dan proteins) on the right side. These flow-dependent asymmetric signals are integrated with bilateral Nodal expression to trigger Nodal signaling exclusively in the left LPM. Embryonic axes: A, anterior; P, posterior; D, dorsal; V, ventral; L, left; R, right.
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Figure 1: Figure 1. Working model for how LR asymmetry is established in vertebrate embryos. (A) Asymmetric Nodal signaling guides asymmetric organ development. The TGFβ signaling molecule Nodal initiates its own expression in left lateral plate mesoderm (LPM) to expand asymmetric patterning along the left side of the embryo and induces expression of Lefty and Pitx2. Lefty molecules function as Nodal antagonists in the embryonic midline (dashed line) and LPM to place boundaries on Nodal signaling. Pitx2 is a transcription factor thought to control genes involved in asymmetric morphogenesis of visceral organs. (B) Asymmetric fluid flow in the ciliated organ of asymmetry is translated into asymmetric Nodal signaling. Motile LR cilia (red) generate a leftward flow that results in increased Ca2+ signals on the left side of the organ of asymmetry and elevated expression of Cerebrus/Dan family Nodal antagonists (Dan proteins) on the right side. These flow-dependent asymmetric signals are integrated with bilateral Nodal expression to trigger Nodal signaling exclusively in the left LPM. Embryonic axes: A, anterior; P, posterior; D, dorsal; V, ventral; L, left; R, right.

Mentions: A groundbreaking advancement of our understanding of LR asymmetry came with the discovery that signaling molecules are asymmetrically expressed along the LR axis in the chicken embryo at developmental stages that precede formation of visceral organs.6 Transient left-sided expression of Sonic hedgehog (Shh) near an embryonic structure called Hensen’s node was found to activate asymmetric expression of cNR-1, a homolog of the mouse Nodal gene that encodes a secreted signaling ligand in the TGF-β superfamily. At subsequent stages, an expansion of cNR-1/Nodal expression was observed exclusively on the left side of the embryo in lateral plate mesoderm (LPM) that contributes to the heart and gut. This revealed that the left and right sides of the embryo are patterned at the molecular level prior to the development of organ asymmetries. While not all molecular asymmetries identified in the chick embryo are conserved (e.g., Shh asymmetry), a left-sided Nodal signaling cascade (Fig. 1A) has been observed in all vertebrate embryos analyzed. Nodal induces its own expression in neighboring cells as well as the expression of Lefty proteins that function as diffusible Nodal antagonists to limit the Nodal expression domain.7 Nodal also activates expression of the transcription factor Pitx2 in left LPM cells. Left-sided Pitx2 expression persists in the developing heart and gut where it regulates genes that mediate asymmetric morphogenesis of these organs (Fig. 1A). Genetic and functional analyses in medaka, zebrafish, frog and mouse8-11 indicate this asymmetric Nodal signaling plays a critical and conserved role in directing LR development of visceral organs.


Salient features of the ciliated organ of asymmetry.

Amack JD - Bioarchitecture (2014)

Figure 1. Working model for how LR asymmetry is established in vertebrate embryos. (A) Asymmetric Nodal signaling guides asymmetric organ development. The TGFβ signaling molecule Nodal initiates its own expression in left lateral plate mesoderm (LPM) to expand asymmetric patterning along the left side of the embryo and induces expression of Lefty and Pitx2. Lefty molecules function as Nodal antagonists in the embryonic midline (dashed line) and LPM to place boundaries on Nodal signaling. Pitx2 is a transcription factor thought to control genes involved in asymmetric morphogenesis of visceral organs. (B) Asymmetric fluid flow in the ciliated organ of asymmetry is translated into asymmetric Nodal signaling. Motile LR cilia (red) generate a leftward flow that results in increased Ca2+ signals on the left side of the organ of asymmetry and elevated expression of Cerebrus/Dan family Nodal antagonists (Dan proteins) on the right side. These flow-dependent asymmetric signals are integrated with bilateral Nodal expression to trigger Nodal signaling exclusively in the left LPM. Embryonic axes: A, anterior; P, posterior; D, dorsal; V, ventral; L, left; R, right.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199803&req=5

Figure 1: Figure 1. Working model for how LR asymmetry is established in vertebrate embryos. (A) Asymmetric Nodal signaling guides asymmetric organ development. The TGFβ signaling molecule Nodal initiates its own expression in left lateral plate mesoderm (LPM) to expand asymmetric patterning along the left side of the embryo and induces expression of Lefty and Pitx2. Lefty molecules function as Nodal antagonists in the embryonic midline (dashed line) and LPM to place boundaries on Nodal signaling. Pitx2 is a transcription factor thought to control genes involved in asymmetric morphogenesis of visceral organs. (B) Asymmetric fluid flow in the ciliated organ of asymmetry is translated into asymmetric Nodal signaling. Motile LR cilia (red) generate a leftward flow that results in increased Ca2+ signals on the left side of the organ of asymmetry and elevated expression of Cerebrus/Dan family Nodal antagonists (Dan proteins) on the right side. These flow-dependent asymmetric signals are integrated with bilateral Nodal expression to trigger Nodal signaling exclusively in the left LPM. Embryonic axes: A, anterior; P, posterior; D, dorsal; V, ventral; L, left; R, right.
Mentions: A groundbreaking advancement of our understanding of LR asymmetry came with the discovery that signaling molecules are asymmetrically expressed along the LR axis in the chicken embryo at developmental stages that precede formation of visceral organs.6 Transient left-sided expression of Sonic hedgehog (Shh) near an embryonic structure called Hensen’s node was found to activate asymmetric expression of cNR-1, a homolog of the mouse Nodal gene that encodes a secreted signaling ligand in the TGF-β superfamily. At subsequent stages, an expansion of cNR-1/Nodal expression was observed exclusively on the left side of the embryo in lateral plate mesoderm (LPM) that contributes to the heart and gut. This revealed that the left and right sides of the embryo are patterned at the molecular level prior to the development of organ asymmetries. While not all molecular asymmetries identified in the chick embryo are conserved (e.g., Shh asymmetry), a left-sided Nodal signaling cascade (Fig. 1A) has been observed in all vertebrate embryos analyzed. Nodal induces its own expression in neighboring cells as well as the expression of Lefty proteins that function as diffusible Nodal antagonists to limit the Nodal expression domain.7 Nodal also activates expression of the transcription factor Pitx2 in left LPM cells. Left-sided Pitx2 expression persists in the developing heart and gut where it regulates genes that mediate asymmetric morphogenesis of these organs (Fig. 1A). Genetic and functional analyses in medaka, zebrafish, frog and mouse8-11 indicate this asymmetric Nodal signaling plays a critical and conserved role in directing LR development of visceral organs.

Bottom Line: These 'LR cilia' are found in the ventral node and posterior notochordal plate in mammals, the gastrocoel roof plate in amphibians and Kupffer's vesicle in teleost fish.I consider these transient ciliated structures as the 'organ of asymmetry' that directs LR patterning of the developing embryo.Variations in size and morphology of the organ of asymmetry in different vertebrate species have raised questions regarding the fundamental features that are required for LR determination.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology; State University of New York; Upstate Medical University; Syracuse, NY USA.

ABSTRACT
Many internal organs develop distinct left and right sides that are essential for their functions. In several vertebrate embryos, motile cilia generate an asymmetric fluid flow that plays an important role in establishing left-right (LR) signaling cascades. These 'LR cilia' are found in the ventral node and posterior notochordal plate in mammals, the gastrocoel roof plate in amphibians and Kupffer's vesicle in teleost fish. I consider these transient ciliated structures as the 'organ of asymmetry' that directs LR patterning of the developing embryo. Variations in size and morphology of the organ of asymmetry in different vertebrate species have raised questions regarding the fundamental features that are required for LR determination. Here, I review current models for how LR asymmetry is established in vertebrates, discuss the cellular architecture of the ciliated organ of asymmetry and then propose key features of this organ that are critical for orienting the LR body axis.

Show MeSH
Related in: MedlinePlus