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Synchronous symmetry breaking in neurons with different neurite counts.

Wissner-Gross ZD, Scott MA, Steinmeyer JD, Yanik MF - PLoS ONE (2013)

Bottom Line: However, the effects of neurite count in neuronal symmetry breaking have never been studied.We also show that despite the significant differences among the previously proposed models, they all agree with our experimental findings when the expression levels of the proteins responsible for symmetry breaking increase with neurite count.Consistent with these results, we observe that the expression levels of two of these proteins, HRas and shootin1, significantly correlate with neurite count.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Harvard University, Cambridge, Massachusetts, USA.

ABSTRACT
As neurons develop, several immature processes (i.e., neurites) grow out of the cell body. Over time, each neuron breaks symmetry when only one of its neurites grows much longer than the rest, becoming an axon. This symmetry breaking is an important step in neurodevelopment, and aberrant symmetry breaking is associated with several neuropsychiatric diseases, including schizophrenia and autism. However, the effects of neurite count in neuronal symmetry breaking have never been studied. Existing models for neuronal polarization disagree: some predict that neurons with more neurites polarize up to several days later than neurons with fewer neurites, while others predict that neurons with different neurite counts polarize synchronously. We experimentally find that neurons with different neurite counts polarize synchronously. We also show that despite the significant differences among the previously proposed models, they all agree with our experimental findings when the expression levels of the proteins responsible for symmetry breaking increase with neurite count. Consistent with these results, we observe that the expression levels of two of these proteins, HRas and shootin1, significantly correlate with neurite count. This coordinated symmetry breaking we observed among neurons with different neurite counts may be important for synchronized polarization of neurons in developing organisms.

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Polarity as a function of time and neurite count as predicted by the three models of neuronal symmetry breaking modified with dynamic neurite counts.Continuous curves were generated by connecting data for each neurite count at different time points. A–C, Polarity vs. time curves for different neurite counts in the Samuels, Fivaz, and Toriyama models with dynamic neurite counts. In the Fivaz model, HRas expression was normalized so that it was independent of neurite count, as in Fig. 3E. D–F, Expression levels of the protein underlying symmetry breaking now increases linearly with neurite count in all three models. In the Fivaz model, this protein is HRas; in the Toriyama model, it is shootin1; and in the Samuels model, “protein” refers to the rate-limiting chemical for neurite growth. Further details on how the Samuels and Toriyama models were modified can be found in the Materials and Methods section.
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pone-0054905-g005: Polarity as a function of time and neurite count as predicted by the three models of neuronal symmetry breaking modified with dynamic neurite counts.Continuous curves were generated by connecting data for each neurite count at different time points. A–C, Polarity vs. time curves for different neurite counts in the Samuels, Fivaz, and Toriyama models with dynamic neurite counts. In the Fivaz model, HRas expression was normalized so that it was independent of neurite count, as in Fig. 3E. D–F, Expression levels of the protein underlying symmetry breaking now increases linearly with neurite count in all three models. In the Fivaz model, this protein is HRas; in the Toriyama model, it is shootin1; and in the Samuels model, “protein” refers to the rate-limiting chemical for neurite growth. Further details on how the Samuels and Toriyama models were modified can be found in the Materials and Methods section.

Mentions: We then modified the Samuels, Fivaz, and Toriyama models by including this “dynamic neurite count” (see Materials and Methods section for further details), thereby making them more biophysically accurate. The addition of a dynamic neurite count increased the polarity of neurons with many neurites in the Samuels model (Fig. 5A) and in the version of the Fivaz model in which HRas expression was independent of neurite count (Fig. 5B) (compare with Figs. 3B and 3E). However, polarization among neurons with different neurite counts remained asynchronous, as the separation between the polarity vs. time curves remained significant. Adding a dynamic neurite count also had little effect on the Toriyama model (Fig. 5C), except to universally delay symmetry breaking in all neurons (compare with Fig. 3D). In summary, we found that a dynamic neurite count was insufficient for explaining the synchronous polarization behavior we observed in neurons with different neurite counts.


Synchronous symmetry breaking in neurons with different neurite counts.

Wissner-Gross ZD, Scott MA, Steinmeyer JD, Yanik MF - PLoS ONE (2013)

Polarity as a function of time and neurite count as predicted by the three models of neuronal symmetry breaking modified with dynamic neurite counts.Continuous curves were generated by connecting data for each neurite count at different time points. A–C, Polarity vs. time curves for different neurite counts in the Samuels, Fivaz, and Toriyama models with dynamic neurite counts. In the Fivaz model, HRas expression was normalized so that it was independent of neurite count, as in Fig. 3E. D–F, Expression levels of the protein underlying symmetry breaking now increases linearly with neurite count in all three models. In the Fivaz model, this protein is HRas; in the Toriyama model, it is shootin1; and in the Samuels model, “protein” refers to the rate-limiting chemical for neurite growth. Further details on how the Samuels and Toriyama models were modified can be found in the Materials and Methods section.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569465&req=5

pone-0054905-g005: Polarity as a function of time and neurite count as predicted by the three models of neuronal symmetry breaking modified with dynamic neurite counts.Continuous curves were generated by connecting data for each neurite count at different time points. A–C, Polarity vs. time curves for different neurite counts in the Samuels, Fivaz, and Toriyama models with dynamic neurite counts. In the Fivaz model, HRas expression was normalized so that it was independent of neurite count, as in Fig. 3E. D–F, Expression levels of the protein underlying symmetry breaking now increases linearly with neurite count in all three models. In the Fivaz model, this protein is HRas; in the Toriyama model, it is shootin1; and in the Samuels model, “protein” refers to the rate-limiting chemical for neurite growth. Further details on how the Samuels and Toriyama models were modified can be found in the Materials and Methods section.
Mentions: We then modified the Samuels, Fivaz, and Toriyama models by including this “dynamic neurite count” (see Materials and Methods section for further details), thereby making them more biophysically accurate. The addition of a dynamic neurite count increased the polarity of neurons with many neurites in the Samuels model (Fig. 5A) and in the version of the Fivaz model in which HRas expression was independent of neurite count (Fig. 5B) (compare with Figs. 3B and 3E). However, polarization among neurons with different neurite counts remained asynchronous, as the separation between the polarity vs. time curves remained significant. Adding a dynamic neurite count also had little effect on the Toriyama model (Fig. 5C), except to universally delay symmetry breaking in all neurons (compare with Fig. 3D). In summary, we found that a dynamic neurite count was insufficient for explaining the synchronous polarization behavior we observed in neurons with different neurite counts.

Bottom Line: However, the effects of neurite count in neuronal symmetry breaking have never been studied.We also show that despite the significant differences among the previously proposed models, they all agree with our experimental findings when the expression levels of the proteins responsible for symmetry breaking increase with neurite count.Consistent with these results, we observe that the expression levels of two of these proteins, HRas and shootin1, significantly correlate with neurite count.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics, Harvard University, Cambridge, Massachusetts, USA.

ABSTRACT
As neurons develop, several immature processes (i.e., neurites) grow out of the cell body. Over time, each neuron breaks symmetry when only one of its neurites grows much longer than the rest, becoming an axon. This symmetry breaking is an important step in neurodevelopment, and aberrant symmetry breaking is associated with several neuropsychiatric diseases, including schizophrenia and autism. However, the effects of neurite count in neuronal symmetry breaking have never been studied. Existing models for neuronal polarization disagree: some predict that neurons with more neurites polarize up to several days later than neurons with fewer neurites, while others predict that neurons with different neurite counts polarize synchronously. We experimentally find that neurons with different neurite counts polarize synchronously. We also show that despite the significant differences among the previously proposed models, they all agree with our experimental findings when the expression levels of the proteins responsible for symmetry breaking increase with neurite count. Consistent with these results, we observe that the expression levels of two of these proteins, HRas and shootin1, significantly correlate with neurite count. This coordinated symmetry breaking we observed among neurons with different neurite counts may be important for synchronized polarization of neurons in developing organisms.

Show MeSH
Related in: MedlinePlus