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Novel function of PIWIL1 in neuronal polarization and migration via regulation of microtubule-associated proteins.

Zhao PP, Yao MJ, Chang SY, Gou LT, Liu MF, Qiu ZL, Yuan XB - Mol Brain (2015)

Bottom Line: Furthermore, we found that PIWIL1 unexpectedly regulates the expression of microtubule-associated proteins in cortical neurons.PIWIL1 regulates neuronal polarization and radial migration partly via modulating the expression of microtubule-associated proteins (MAPs).Our finding of PIWIL1's function in neuronal development implies conserved functions of molecules participating in morphogenesis of brain and germline tissue and provides a mechanism as to how mutations of PIWI may be associated with autism.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

ABSTRACT

Background: Young neurons in the developing brain establish a polarized morphology for proper migration. The PIWI family of piRNA processing proteins are considered to be restrictively expressed in germline tissues and several types of cancer cells. They play important roles in spermatogenesis, stem cell maintenance, piRNA biogenesis, and transposon silencing. Interestingly a recent study showed that de novo mutations of PIWI family members are strongly associated with autism.

Results: Here, we report that PIWI-like 1 (PIWIL1), a PIWI family member known to be essential for the transition of round spermatid into elongated spermatid, plays a role in the polarization and radial migration of newborn neurons in the developing cerebral cortex. Knocking down PIWIL1 in newborn cortical neurons by in utero electroporation of specific siRNAs resulted in retardation of the transition of neurons from the multipolar stage to the bipolar stage followed by a defect in their radial migration to the proper destination. Domain analysis showed that both the RNA binding PAZ domain and the RNA processing PIWI domain in PIWIL1 were indispensable for its function in neuronal migration. Furthermore, we found that PIWIL1 unexpectedly regulates the expression of microtubule-associated proteins in cortical neurons.

Conclusions: PIWIL1 regulates neuronal polarization and radial migration partly via modulating the expression of microtubule-associated proteins (MAPs). Our finding of PIWIL1's function in neuronal development implies conserved functions of molecules participating in morphogenesis of brain and germline tissue and provides a mechanism as to how mutations of PIWI may be associated with autism.

No MeSH data available.


Related in: MedlinePlus

PIWIL1 is required for the multipolar–bipolar transition of postmitotic neurons. a, d Morphology of labeled neurons in different cortical regions 3 or 5 days post-IUE with siRNA 1. b, e Traces of labeled neurons 3 or 5 days after IUE respectively.c, f Percentage of bipolar cells (white arrows) in different cortical regions. Data are from at least 3 independent IUE experiments. g Typical morphology of labeled mouse neurons in the IZ 3 days after IUE with RNAi 2 or RNAi 2 plus HIWI compared with individual control plasmid. h Percentage of bipolar cells at the IZ of electroporated mouse cortex. Scale bar, 30 μm. Error bar, SEM, **P < 0.01, ***P < 0.001 (Student’s t-test)
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Fig2: PIWIL1 is required for the multipolar–bipolar transition of postmitotic neurons. a, d Morphology of labeled neurons in different cortical regions 3 or 5 days post-IUE with siRNA 1. b, e Traces of labeled neurons 3 or 5 days after IUE respectively.c, f Percentage of bipolar cells (white arrows) in different cortical regions. Data are from at least 3 independent IUE experiments. g Typical morphology of labeled mouse neurons in the IZ 3 days after IUE with RNAi 2 or RNAi 2 plus HIWI compared with individual control plasmid. h Percentage of bipolar cells at the IZ of electroporated mouse cortex. Scale bar, 30 μm. Error bar, SEM, **P < 0.01, ***P < 0.001 (Student’s t-test)

Mentions: Newborn neurons produced at the VZ of developing cerebral cortex will first experience a multipolar stage with several minor processes extending from the soma and then gradually establish a bipolar morphology with one elongated neurite that leads the migration of the neuron towards the surface of the CP [1]. To analyze whether neuronal polarization defects precedes the retardation of neuronal migration, we traced the morphology of newborn neurons 3 to 5 days after IUE of rat embryos and quantified the percentages of bipolar and multipolar cells. Most cells (~70 %) in the IZ had established a bipolar morphology 3 days after IUE with Scramble, but less than 30 % of labeled cells had established bipoplar morphology in RNAi 1- or RNAi 4-transfected brains (Fig. 2a-c). Five days after IUE, most cells had migrated into the CP in control brains, whereas in RNAi 1- or RNAi 4-transfected brains, most cells were arrested at the IZ and maintained a multipolar morphology (Fig. 2d-f). IUE of PIWIL1 siRNA (RNAi 2) in mouse brains caused a similar defect in neuronal polarization, which could be rescued by co-expression of HIWI (Fig. 2g and h).Fig. 2


Novel function of PIWIL1 in neuronal polarization and migration via regulation of microtubule-associated proteins.

Zhao PP, Yao MJ, Chang SY, Gou LT, Liu MF, Qiu ZL, Yuan XB - Mol Brain (2015)

PIWIL1 is required for the multipolar–bipolar transition of postmitotic neurons. a, d Morphology of labeled neurons in different cortical regions 3 or 5 days post-IUE with siRNA 1. b, e Traces of labeled neurons 3 or 5 days after IUE respectively.c, f Percentage of bipolar cells (white arrows) in different cortical regions. Data are from at least 3 independent IUE experiments. g Typical morphology of labeled mouse neurons in the IZ 3 days after IUE with RNAi 2 or RNAi 2 plus HIWI compared with individual control plasmid. h Percentage of bipolar cells at the IZ of electroporated mouse cortex. Scale bar, 30 μm. Error bar, SEM, **P < 0.01, ***P < 0.001 (Student’s t-test)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4477296&req=5

Fig2: PIWIL1 is required for the multipolar–bipolar transition of postmitotic neurons. a, d Morphology of labeled neurons in different cortical regions 3 or 5 days post-IUE with siRNA 1. b, e Traces of labeled neurons 3 or 5 days after IUE respectively.c, f Percentage of bipolar cells (white arrows) in different cortical regions. Data are from at least 3 independent IUE experiments. g Typical morphology of labeled mouse neurons in the IZ 3 days after IUE with RNAi 2 or RNAi 2 plus HIWI compared with individual control plasmid. h Percentage of bipolar cells at the IZ of electroporated mouse cortex. Scale bar, 30 μm. Error bar, SEM, **P < 0.01, ***P < 0.001 (Student’s t-test)
Mentions: Newborn neurons produced at the VZ of developing cerebral cortex will first experience a multipolar stage with several minor processes extending from the soma and then gradually establish a bipolar morphology with one elongated neurite that leads the migration of the neuron towards the surface of the CP [1]. To analyze whether neuronal polarization defects precedes the retardation of neuronal migration, we traced the morphology of newborn neurons 3 to 5 days after IUE of rat embryos and quantified the percentages of bipolar and multipolar cells. Most cells (~70 %) in the IZ had established a bipolar morphology 3 days after IUE with Scramble, but less than 30 % of labeled cells had established bipoplar morphology in RNAi 1- or RNAi 4-transfected brains (Fig. 2a-c). Five days after IUE, most cells had migrated into the CP in control brains, whereas in RNAi 1- or RNAi 4-transfected brains, most cells were arrested at the IZ and maintained a multipolar morphology (Fig. 2d-f). IUE of PIWIL1 siRNA (RNAi 2) in mouse brains caused a similar defect in neuronal polarization, which could be rescued by co-expression of HIWI (Fig. 2g and h).Fig. 2

Bottom Line: Furthermore, we found that PIWIL1 unexpectedly regulates the expression of microtubule-associated proteins in cortical neurons.PIWIL1 regulates neuronal polarization and radial migration partly via modulating the expression of microtubule-associated proteins (MAPs).Our finding of PIWIL1's function in neuronal development implies conserved functions of molecules participating in morphogenesis of brain and germline tissue and provides a mechanism as to how mutations of PIWI may be associated with autism.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

ABSTRACT

Background: Young neurons in the developing brain establish a polarized morphology for proper migration. The PIWI family of piRNA processing proteins are considered to be restrictively expressed in germline tissues and several types of cancer cells. They play important roles in spermatogenesis, stem cell maintenance, piRNA biogenesis, and transposon silencing. Interestingly a recent study showed that de novo mutations of PIWI family members are strongly associated with autism.

Results: Here, we report that PIWI-like 1 (PIWIL1), a PIWI family member known to be essential for the transition of round spermatid into elongated spermatid, plays a role in the polarization and radial migration of newborn neurons in the developing cerebral cortex. Knocking down PIWIL1 in newborn cortical neurons by in utero electroporation of specific siRNAs resulted in retardation of the transition of neurons from the multipolar stage to the bipolar stage followed by a defect in their radial migration to the proper destination. Domain analysis showed that both the RNA binding PAZ domain and the RNA processing PIWI domain in PIWIL1 were indispensable for its function in neuronal migration. Furthermore, we found that PIWIL1 unexpectedly regulates the expression of microtubule-associated proteins in cortical neurons.

Conclusions: PIWIL1 regulates neuronal polarization and radial migration partly via modulating the expression of microtubule-associated proteins (MAPs). Our finding of PIWIL1's function in neuronal development implies conserved functions of molecules participating in morphogenesis of brain and germline tissue and provides a mechanism as to how mutations of PIWI may be associated with autism.

No MeSH data available.


Related in: MedlinePlus