title: Wnt1-cre-mediated conditional loss of Dicer results in malformation of the midbrain and cerebellum and failure of neural crest and dopaminergic differentiation in mice.
abstract: The involvement of microRNAs (miRNAs) in the development of the neural crest (NC) cells and other neuronal differentiation is still poorly understood. Here, we investigated the global function of miRNAs in embryonic development by examining the Wnt1-cre-mediated Dicer knockout mice. Dicer ablation resulted in malformation of the midbrain and cerebellum and failure of NC and dopaminergic differentiation. First, the Dicer mutant fetuses exhibited dramatic malformation of the tectum and cerebellum and the eyelids were open. Second, the skeletal structures that are derived from the cranial NC were lost or mostly ablated in Dicer mutant mice. Third, deletion of Dicer in the NC cells resulted in the malformation of the dorsal root ganglia, enteric nervous system and sympathetic ganglia. Interestingly, the expression of neuropeptide Y and its potential regulators TrkA, AP-2alpha and AP-2beta was largely abolished in sympathetic neurons of Dicer mutant mice. Fourth, in situ hybridization data revealed that the expression of miR-9, miR-124 and miR-218 in the midbrain and rostral hindbrain area was mostly eliminated in the Dicer mutant mice. We then demonstrated that the development of dopaminergic neurons was impaired in Dicer-deleted mice. Our studies therefore suggest that miRNAs contribute to the embryonic development in multiple locations.
authors.affiliation: State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Huang
authors.forename: Yueguang
authors.initials: Y
authors.lastname: Liu
authors.forename: Menggui
authors.initials: M
authors.lastname: Huang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhao
authors.forename: Leping
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002531:Cerebellum / Q000002:abnormalities* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D047108:Embryonic Development; D004722:Endoribonucleases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D017404:In Situ Hybridization, Fluorescence; D019426:Integrases / Q000378:metabolism*; D008636:Mesencephalon / Q000002:abnormalities* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism; D009432:Neural Crest / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D043244:Ribonuclease III; D050656:Transcription Factor AP-2 / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics*
chemical_list: C547684:MIRN218 microRNA, mouse; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D009478:Neuropeptide Y; D050656:Transcription Factor AP-2; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D020917:Receptor, trkA; C045073:Cre recombinase; D019426:Integrases; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D004298:Dopamine