Study reveals new mechanism of cell autonomy to regulate the polarization of cortex neurons

The international academic journal Cell Reports published the research paper "Wdr47 controls neuronal polarization through the Camsap family microtubule minus-end-binding", published online by zhu Xueliang Research Group of the Center for Excellence in Molecular Cell Science (Institute of Biochemistry and Cell Biology) of the Chinese Academy of SciencesThe study revealed that the Wdr47 protein selectively regulates microtubule dynamics by affecting the subcellular positioning of the Camsap family protein, thereby regulating the polarization of the cortex neurons during embryonic developmentNeurons (nerve cells) are the basic structure and functional units of the nervous systemThey usually have several short, thick dendrites and a long, thin axon for receiving and exporting biological signals, respectivelyTherefore, neurons are highly polar, both in form and functionAbnormal neuronal development can lead to mental or motor disordersThe process of building aden-axonic polarity is called neuronpolarizationIn the late middle and late stages of cerebral cortex development in mouse embryos, the vast majority of dermis onthes (cone neurons) are born in the ventricle region through asymmetrical division of radioactive glial cells and migrate strucies along the radial protrusions of glial cells toward specific areas of the outer cortexDuring migration, they undergo a morphological shift from "multipolarity" to "bipolarity" and then develop dendritic and axonsIn vitro isolated cultured cortical neurons can also develop and form multiple dendrites and single axons, indicating that they have a set of cell-autonomous mechanisms to establish and maintain polarityThe dynamic change of microtube is the effector of cell morphology in the process of neuron polarization, and changing the dynamic or arrangement of the microtube is sufficient to affect the polarization process of neuronHowever, only a few microtube regulators currently play a role in neuronal polarization both in and out of the body, and it is not clear how they work together within cellsWdr47 is a protein with WD40 repeating domain that is highly expressed in the central nervous systemIn the study, researchers demonstrated that Wdr47 was a key cell autonomic regulator for the polarization of the cortex neurons, combined with gene knockout, intrauterine embryo electrotransfer, and in vitro neuron cultureWdr47 gene deletion causes respiratory distress and death in newborn mice at individual levels, causes brain white matter fibrosis in sufficiency, lateral ventricle expansion, and cortex stratification disorders at tissue levels, inhibits radial migration and "multipolarity- bipolar" transition of cortisco neurons at the cellular level, and causes in vitro cultured neurons to grow multiple altruistic axesFurther research suggests that Wdr47 regulates neuronal polarization by affecting the microtube skeleton: its gene loss reduces the dynamics of the microtubes facing the ends of the early nerve protrusions of polarization, while overexpression in wild neurons inhibits the elongation of nerve protrusions and the differentiation of axons, as well as the excessive growth and hyperactivity of neurocytosis induced by the low-dose microtube stabilizer, TaxolTo find out the mechanism, the researchers analyzed the interaction of Wdr47's interaction proteomics using immunosemitic precipitation and mass spectrometry techniques, and found that Wdr47 can interact with the microtube negative-end binding protein Camsap family, and can co-organize microtube network structure with Camsap3, and the gene deficiency of Camsap3 has been reported to cause neurons to grow multiple axons The absence of Wdr47 did not cause changes in the overall protein expression of the Camsap family, but the subcellular positioning level affected the accumulation of Camsap3 in early polarization nerve protrusions Moreover, the overexpression of Camsap1 or 3 can save the neuronal polarization defect phenotype caused by Wdr47 loss in an inviving system The above results show that in the early stage of neuronpolarization, Wdr47, through interaction with the Camsap protein family, finely regulates the dynamicand and network structure of the local microspheres of the cell, and promotes the proper dynamic remodeling of nerve protrusions, thus ensuring the smooth progress of the polarization process The findings will help to better understand the control mechanism of neuronal axon growth and differentiation, as well as the pathogenesis of neonatal respiratory distress and related neurological diseases (BioValleyBioon.com)