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Role of the gut endoderm in relaying left-right patterning in mice.

Viotti M, Niu L, Shi SH, Hadjantonakis AK - PLoS Biol. (2012)

Bottom Line: Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos.They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo.The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, New York, United States of America.

ABSTRACT
Establishment of left-right (LR) asymmetry occurs after gastrulation commences and utilizes a conserved cascade of events. In the mouse, LR symmetry is broken at a midline structure, the node, and involves signal relay to the lateral plate, where it results in asymmetric organ morphogenesis. How information transmits from the node to the distantly situated lateral plate remains unclear. Noting that embryos lacking Sox17 exhibit defects in both gut endoderm formation and LR patterning, we investigated a potential connection between these two processes. We observed an endoderm-specific absence of the critical gap junction component, Connexin43 (Cx43), in Sox17 mutants. Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos. They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo. The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype. Collectively, our data demonstrate that Cx43-mediated communication across gap junctions within the gut endoderm serves as a mechanism for information relay between node and lateral plate in a process that is critical for the establishment of LR asymmetry in mice.

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Working model for role of gut endoderm in LR asymmetry establishment.Sox17 regulates morphogenesis of the gut endoderm, whose cellular interfaces contain Cx43-comprised gap junctions. After LR symmetry is broken in the node by rotating cilia, the resulting nodal flow induces left-biased asymmetries around the node. These asymmetries are transmitted via gap junction communication within the gut endoderm to the target tissue, the left LPM, where the Nodal/Lefty2/Pitx2 asymmetry cascade is activated.
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pbio-1001276-g008: Working model for role of gut endoderm in LR asymmetry establishment.Sox17 regulates morphogenesis of the gut endoderm, whose cellular interfaces contain Cx43-comprised gap junctions. After LR symmetry is broken in the node by rotating cilia, the resulting nodal flow induces left-biased asymmetries around the node. These asymmetries are transmitted via gap junction communication within the gut endoderm to the target tissue, the left LPM, where the Nodal/Lefty2/Pitx2 asymmetry cascade is activated.

Mentions: A cascade of events establishes LR asymmetry in mice. A central unresolved question in this process is the nature of the step between symmetry-breaking at the midline and the tissues executing asymmetric morphogenesis at the lateral plate. To date, mouse mutants exhibiting LR patterning defects fall into three categories based on their expected site of gene function: the node, the LPM, and the midline [8]. No mutant affecting LR asymmetry has been reported to act within the gut endoderm, a tissue situated between the site of symmetry-breaking (the node) and the effector tissue of asymmetric morphogenesis (the lateral plate). Our studies reveal Cx43-mediated communication through gap junctions across the gut endoderm epithelium as a mechanism for information relay between node and LPM in the establishment of LR asymmetry in mice (for model, see Figure 8).


Role of the gut endoderm in relaying left-right patterning in mice.

Viotti M, Niu L, Shi SH, Hadjantonakis AK - PLoS Biol. (2012)

Working model for role of gut endoderm in LR asymmetry establishment.Sox17 regulates morphogenesis of the gut endoderm, whose cellular interfaces contain Cx43-comprised gap junctions. After LR symmetry is broken in the node by rotating cilia, the resulting nodal flow induces left-biased asymmetries around the node. These asymmetries are transmitted via gap junction communication within the gut endoderm to the target tissue, the left LPM, where the Nodal/Lefty2/Pitx2 asymmetry cascade is activated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3295824&req=5

pbio-1001276-g008: Working model for role of gut endoderm in LR asymmetry establishment.Sox17 regulates morphogenesis of the gut endoderm, whose cellular interfaces contain Cx43-comprised gap junctions. After LR symmetry is broken in the node by rotating cilia, the resulting nodal flow induces left-biased asymmetries around the node. These asymmetries are transmitted via gap junction communication within the gut endoderm to the target tissue, the left LPM, where the Nodal/Lefty2/Pitx2 asymmetry cascade is activated.
Mentions: A cascade of events establishes LR asymmetry in mice. A central unresolved question in this process is the nature of the step between symmetry-breaking at the midline and the tissues executing asymmetric morphogenesis at the lateral plate. To date, mouse mutants exhibiting LR patterning defects fall into three categories based on their expected site of gene function: the node, the LPM, and the midline [8]. No mutant affecting LR asymmetry has been reported to act within the gut endoderm, a tissue situated between the site of symmetry-breaking (the node) and the effector tissue of asymmetric morphogenesis (the lateral plate). Our studies reveal Cx43-mediated communication through gap junctions across the gut endoderm epithelium as a mechanism for information relay between node and LPM in the establishment of LR asymmetry in mice (for model, see Figure 8).

Bottom Line: Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos.They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo.The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype.

View Article: PubMed Central - PubMed

Affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York, New York, United States of America.

ABSTRACT
Establishment of left-right (LR) asymmetry occurs after gastrulation commences and utilizes a conserved cascade of events. In the mouse, LR symmetry is broken at a midline structure, the node, and involves signal relay to the lateral plate, where it results in asymmetric organ morphogenesis. How information transmits from the node to the distantly situated lateral plate remains unclear. Noting that embryos lacking Sox17 exhibit defects in both gut endoderm formation and LR patterning, we investigated a potential connection between these two processes. We observed an endoderm-specific absence of the critical gap junction component, Connexin43 (Cx43), in Sox17 mutants. Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos. They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo. The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype. Collectively, our data demonstrate that Cx43-mediated communication across gap junctions within the gut endoderm serves as a mechanism for information relay between node and lateral plate in a process that is critical for the establishment of LR asymmetry in mice.

Show MeSH
Related in: MedlinePlus