Limits...
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.

Show MeSH

Related in: MedlinePlus

HRas and shootin1 expression in developing hippocampal neurons as a function of neurite count after 40 h in culture.A, Typical immunocytochemical stain for HRas in a neuron with 5 neurites. B, Typical immunocytochemical stain for shootin1 in a neuron with 3 neurites. The brightness in both A and B were saturated to make the neurites more visible. When these images were analyzed to determine relative HRas and shootin1 expression levels, image brightness was kept unsaturated. C–D, HRas/shootin1 expression as a function of neurite count. Individual neurons are indicated by plus signs, while the solid line indicates linear fits to the data. In both trend lines, the slope was significantly positive (p < 10−4 for both fits).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3569465&req=5

pone-0054905-g006: HRas and shootin1 expression in developing hippocampal neurons as a function of neurite count after 40 h in culture.A, Typical immunocytochemical stain for HRas in a neuron with 5 neurites. B, Typical immunocytochemical stain for shootin1 in a neuron with 3 neurites. The brightness in both A and B were saturated to make the neurites more visible. When these images were analyzed to determine relative HRas and shootin1 expression levels, image brightness was kept unsaturated. C–D, HRas/shootin1 expression as a function of neurite count. Individual neurons are indicated by plus signs, while the solid line indicates linear fits to the data. In both trend lines, the slope was significantly positive (p < 10−4 for both fits).

Mentions: Finally, we tested our hypothesis that HRas and/or shootin1 expression levels increase with neurite count. To do this, we performed immunocytochemical stains of hippocampal neurons cultured for 40 h, and then calculated the relative fluorescence of approximately 150 neurons for each stain, recording neurite count as well. Figs. 6A–B show sample stains for HRas and shootin1, respectively. We found that both HRas and shootin1 expression significantly increased with neurite count (Figs. 6C–D, see Table S2 for more information).


Synchronous symmetry breaking in neurons with different neurite counts.

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

HRas and shootin1 expression in developing hippocampal neurons as a function of neurite count after 40 h in culture.A, Typical immunocytochemical stain for HRas in a neuron with 5 neurites. B, Typical immunocytochemical stain for shootin1 in a neuron with 3 neurites. The brightness in both A and B were saturated to make the neurites more visible. When these images were analyzed to determine relative HRas and shootin1 expression levels, image brightness was kept unsaturated. C–D, HRas/shootin1 expression as a function of neurite count. Individual neurons are indicated by plus signs, while the solid line indicates linear fits to the data. In both trend lines, the slope was significantly positive (p < 10−4 for both fits).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569465&req=5

pone-0054905-g006: HRas and shootin1 expression in developing hippocampal neurons as a function of neurite count after 40 h in culture.A, Typical immunocytochemical stain for HRas in a neuron with 5 neurites. B, Typical immunocytochemical stain for shootin1 in a neuron with 3 neurites. The brightness in both A and B were saturated to make the neurites more visible. When these images were analyzed to determine relative HRas and shootin1 expression levels, image brightness was kept unsaturated. C–D, HRas/shootin1 expression as a function of neurite count. Individual neurons are indicated by plus signs, while the solid line indicates linear fits to the data. In both trend lines, the slope was significantly positive (p < 10−4 for both fits).
Mentions: Finally, we tested our hypothesis that HRas and/or shootin1 expression levels increase with neurite count. To do this, we performed immunocytochemical stains of hippocampal neurons cultured for 40 h, and then calculated the relative fluorescence of approximately 150 neurons for each stain, recording neurite count as well. Figs. 6A–B show sample stains for HRas and shootin1, respectively. We found that both HRas and shootin1 expression significantly increased with neurite count (Figs. 6C–D, see Table S2 for more information).

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