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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

Identification of PIWIL1 target genes. a Strategy for identifying target genes. b Fold changes of the mRNA levels of several MAPs based on mRNA sequencing results. c, d Western blots showing the reduction of MAP1B, MAP2, and Tau, but not DCX, by PIWIL1 knockdown in cultured cortical neurons. Error bar, SEM. *P < 0.05, **P < 0.01 (Student’s t-test)
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Fig4: Identification of PIWIL1 target genes. a Strategy for identifying target genes. b Fold changes of the mRNA levels of several MAPs based on mRNA sequencing results. c, d Western blots showing the reduction of MAP1B, MAP2, and Tau, but not DCX, by PIWIL1 knockdown in cultured cortical neurons. Error bar, SEM. *P < 0.05, **P < 0.01 (Student’s t-test)

Mentions: To elucidate the target genes of PIWIL1, we used deep sequencing to compare the mRNA profiles of cultured cortical neurons 48 h after they were electroporated with control and PIWIL1 siRNAs (GEO No. GSE48236) (Fig. 4a). With PIWIL1 knockdown, 286 genes were upregulated and 667 genes were downregulated (FDR ≤ 0.05, /log2Ratio/ ≥ 0.58). Gene ontology (GO) analysis of the group of 667 downregulated genes showed significant enrichment of GO terms related to cytoskeleton organization, especially the microtubule organization (Additional file 6: Table S1). GO analysis of the group of 286 upregulated genes showed significant enrichment of GO terms related to protein transport and establishement of protein localization (Additional file 7: Table S2).Fig. 4


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)

Identification of PIWIL1 target genes. a Strategy for identifying target genes. b Fold changes of the mRNA levels of several MAPs based on mRNA sequencing results. c, d Western blots showing the reduction of MAP1B, MAP2, and Tau, but not DCX, by PIWIL1 knockdown in cultured cortical neurons. Error bar, SEM. *P < 0.05, **P < 0.01 (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

Fig4: Identification of PIWIL1 target genes. a Strategy for identifying target genes. b Fold changes of the mRNA levels of several MAPs based on mRNA sequencing results. c, d Western blots showing the reduction of MAP1B, MAP2, and Tau, but not DCX, by PIWIL1 knockdown in cultured cortical neurons. Error bar, SEM. *P < 0.05, **P < 0.01 (Student’s t-test)
Mentions: To elucidate the target genes of PIWIL1, we used deep sequencing to compare the mRNA profiles of cultured cortical neurons 48 h after they were electroporated with control and PIWIL1 siRNAs (GEO No. GSE48236) (Fig. 4a). With PIWIL1 knockdown, 286 genes were upregulated and 667 genes were downregulated (FDR ≤ 0.05, /log2Ratio/ ≥ 0.58). Gene ontology (GO) analysis of the group of 667 downregulated genes showed significant enrichment of GO terms related to cytoskeleton organization, especially the microtubule organization (Additional file 6: Table S1). GO analysis of the group of 286 upregulated genes showed significant enrichment of GO terms related to protein transport and establishement of protein localization (Additional file 7: Table S2).Fig. 4

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