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Polarity and arrangement of the columns |
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Neurons gather to form a column showing a regular morphology, and multiple columns are precisely arranged in the brain. The mechanisms that control the morphology and arrangement of the columns are unknown. In contrast, molecular mechanisms that control the planar cell polarity (PCP) in epithelial tissues have been extensicely studied. We demonstrated that molecules that are shared with the PCP system control the morphology and arrangement of the columns.
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| The PCP signal controls the polarity of epithelial cells |
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In epithelial tissues such as the fly wing, cells are precisely arranged, and each cell shows a planar polarity. For example, the hairs of the wing cells are distally oriented. Since the columns are made from multiple neurons and establish the higher order brain functions, the polarity and arrangement of the columns must also be regulated by a similar molecular mechanism. In the epithelial cells. molecules such as Fmi, Fz and Vang regulate the PCP.
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| Shape and arrangement of the columns are regulated by the PCP factors |
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In epithelial tissues, Fmi plays a central role in PCP. We uncovered that Fmi is localized to the columns showing the donut-like pattern (left, middle). Additionally, abnormal morphology and arrangement of the columns were observed in PCP factor mutants such as dishevelled and frizzled (right).
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Wnt ligand gradient controls the shape and arrangement of the columns
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In general, the PCP factors are regulated under the control of the gradient of extracellular Wnt ligands. Among seven fly Wnt ligands, DWnt4 is expressed in the ventral brain, while DWnt10 is expressed in the dorsal brain (left upper). In DWnt4 mutant brains, the column shape and arrangement are disorganized throughout the brain. In contrast, the mutant phenotype of DWnt10 was only found in the dorsal brain, suggesting that DWnt4 has a long range influence compared with DWnt10.
Additionally, we found that neurites show a particular orientation within the columns. The abnormality in the neurites may cause the abnormal morphology and arrangement of the columns (right). |
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The gradients of DWnt4 and DWnt10 control the shape and arrangement of the columns
It is not clear if the columns in the human brain also have a planar polarity. However, the Wnt/PCP signaling is evolutionarily conserved from fly to human. The findings of this study may also be applied to the columns in the human brain, and play important roles in brain development.
Wang, M., Han, X., Liu, C., Takayama, R., Yasugi, T., Ei, S., Nagayama, M., Tanaka, Y. and Sato, M.
Intracellular trafficking of Notch orchestrates temporal dynamics of Notch activity in the fly brain.
Nature Communications 12, 2083 (2021). |
