Symmetry Breaking and Cortical Rotation
Encyclopedia
The origin of asymmetry in cell division, cell polarity and the mechanism that breaks the symmetry continue to be topics of intense research. Since the early 1990s, many discoveries have been made leading to a sound model of the mechanism for symmetry breaking. This article will focus solely on symmetry breaking in the Xenopus
embryo, an animal model that has wide application. Cortical rotation is a phenomenon that seems to be limited to Xenopus and few ancient teleosts, however the underlying mechanisms of cortical rotation have conserved elements that are found in other chordates. Research in this area is on-going and changes to the model described below are to be expected.
A sperm can bind a Xenopus egg at any position of the pigmented animal hemisphere; however once bound this position then determines the dorsal side of the animal. The dorsal side of the egg is always directly opposite the sperm entry point. The reason being the sperm's centriole acts as an organizing center for the egg’s microtubules. While this observation has been known for quite some time, the question of how all of this works is more complicated. The molecular mechanisms driving dorsal-ventral asymmetry are a fine example of simplicity and complexity inherent in biology.
To identify these elements, researchers looked for mRNA and protein that demonstrated localization to either the vegetal pole or the dorsal side of the embryo to find candidates. The early candidates for the determinant were β-catenin and disheveled (Dsh) . When maternal β-catenin mRNA was degraded in the oocyte, the resulting embryo developed into mutant ventral phenotype and this could be rescued by injecting the fertilized egg with β-catenin mRNA. β-catenin is obversed to be enriched in the dorsal side of the embryo following cortical rotation. The Dsh protein was fused to a GFP and tracked during cortical rotation, it was observed to be in vesicles that were couriered along microtubules to the dorsal side. This led researchers to look into other candidates of the Wnt pathway. Wnt 11 was found to be located specifically at the vegetal pole prior to cortical rotation and is moved to the dorsal side where it activates the wnt signaling pathway . VegT, a T-box transcription factor, is localized to the vegetal cortex and upon cortical rotation is released in a gradient fashion into the embryo to regulate mesoderm development. VegT activates Wnt expression, so while not acted on or moved during cortical rotation, it is active in dorsal-ventral axis formation.
The question still remains, how are these molecules being moved to the dorsal side? This is still not completely known, however evidence suggests that microtubule bundles within the cortex are interacting with kinesin (plus-end directed) motors to become organized into parallel arrays within the cortex and this motion of the motors is the cause of the rotation of the cortex. Also unclear is whether Wnt 11 is the main dorsal determinant or is β-catenin also required, as these two molecules have both been demonstrated to be necessary and sufficient for dorsal development. This along with all of the other factors are important for activating Nodal genes that propagate normal dorsoventral development.
For reviews of the general topic see .
Xenopus
Xenopus is a genus of highly aquatic frogs native to Sub-Saharan Africa. There are 19 species in the Xenopus genus...
embryo, an animal model that has wide application. Cortical rotation is a phenomenon that seems to be limited to Xenopus and few ancient teleosts, however the underlying mechanisms of cortical rotation have conserved elements that are found in other chordates. Research in this area is on-going and changes to the model described below are to be expected.
A sperm can bind a Xenopus egg at any position of the pigmented animal hemisphere; however once bound this position then determines the dorsal side of the animal. The dorsal side of the egg is always directly opposite the sperm entry point. The reason being the sperm's centriole acts as an organizing center for the egg’s microtubules. While this observation has been known for quite some time, the question of how all of this works is more complicated. The molecular mechanisms driving dorsal-ventral asymmetry are a fine example of simplicity and complexity inherent in biology.
Molecular mechanisms
A series of experiments utilizing UV irradiation, cold temperature and pressure (all of which cause microtubule depolymerization) demonstrated that without polymerized microtubules cortical rotation did not occur and resulted in a mutant ventral phenotype. Another study also revealed that mutant phenotype could be rescued (returned to normal) by physically turning the embryo, thus mimicking cortical rotation and demonstrating that microtubules were not the determinant of dorsal development.. From this it was hypothesized that there were other elements within the embryo being moved during cortical rotation.To identify these elements, researchers looked for mRNA and protein that demonstrated localization to either the vegetal pole or the dorsal side of the embryo to find candidates. The early candidates for the determinant were β-catenin and disheveled (Dsh) . When maternal β-catenin mRNA was degraded in the oocyte, the resulting embryo developed into mutant ventral phenotype and this could be rescued by injecting the fertilized egg with β-catenin mRNA. β-catenin is obversed to be enriched in the dorsal side of the embryo following cortical rotation. The Dsh protein was fused to a GFP and tracked during cortical rotation, it was observed to be in vesicles that were couriered along microtubules to the dorsal side. This led researchers to look into other candidates of the Wnt pathway. Wnt 11 was found to be located specifically at the vegetal pole prior to cortical rotation and is moved to the dorsal side where it activates the wnt signaling pathway . VegT, a T-box transcription factor, is localized to the vegetal cortex and upon cortical rotation is released in a gradient fashion into the embryo to regulate mesoderm development. VegT activates Wnt expression, so while not acted on or moved during cortical rotation, it is active in dorsal-ventral axis formation.
The question still remains, how are these molecules being moved to the dorsal side? This is still not completely known, however evidence suggests that microtubule bundles within the cortex are interacting with kinesin (plus-end directed) motors to become organized into parallel arrays within the cortex and this motion of the motors is the cause of the rotation of the cortex. Also unclear is whether Wnt 11 is the main dorsal determinant or is β-catenin also required, as these two molecules have both been demonstrated to be necessary and sufficient for dorsal development. This along with all of the other factors are important for activating Nodal genes that propagate normal dorsoventral development.
For reviews of the general topic see .