title: Novel function of PIWIL1 in neuronal polarization and migration via regulation of microtubule-associated proteins.
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.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.|Graduate School of Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Zhao
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.|Graduate School of Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Mao-Jin
authors.initials: MJ
authors.lastname: Yao
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.|Graduate School of Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Graduate School of Chinese Academy of Sciences, Shanghai, 200031, China.|State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Lan-Tao
authors.initials: LT
authors.lastname: Gou
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Mo-Fang
authors.initials: MF
authors.lastname: Liu
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Zi-Long
authors.initials: ZL
authors.lastname: Qiu
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. xyuan@hussmanautism.org.|Current Affiliation: Hussman Institute for Autism, Baltimore, MD, 21201, USA. xyuan@hussmanautism.org.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Yuan
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism*; D002465:Cell Movement; D016764:Cell Polarity; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008938:Mitosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020871:RNA Stability; D017207:Rats, Sprague-Dawley
chemical_list: D060565:Argonaute Proteins; D008869:Microtubule-Associated Proteins; C000606245:PIWIL1 protein, rat; C448522:Piwil1 protein, mouse