Interaction between Oc-1 and Lmx1a promotes ventral midbrain dopamine neural stem cells differentiation into dopamine neurons.
Recent studies have shown that Onecut (Oc) transcription factors may be involved in the early development of midbrain dopaminergic neurons (mdDA). The expression profile of Oc factors matches that of Lmx1a, an important intrinsic transcription factor in the development of mDA neuron. Moreover, the Wnt1-Lmx1a pathway controls the mdDA differentiation. However, their expression dynamics and molecular mechanisms remain to be determined. To address these issues, we hypothesize that cross-talk between Oc-1 and Lmx1a regulates the mdDA specification and differentiation through the canonical Wnt-β-catenin pathway. We found that Oc-1 and Lmx1a displayed a very similar expression profile from embryonic to adult ventral midbrain (VM) tissues. Oc-1 regulated the proliferation and differentiation of ventral midbrain neural stem cells (vmNSCs). Downregulation of Oc-1 decreased both transcript and protein level of Lmx1a. Oc-1 interacted with lmx1a in vmNSCs in vitro and in VM tissues in vivo. Knockdown of Lmx1a reduced the expression of Oc-1 and Wnt1 in vmNSCs. Inhibiting Wnt1 signaling in vmNSCs provoked similar responses. Our data suggested that Oc-1 interacts with Lmx1a to promote vmNSCs differentiation into dopamine neuron through Wnt1-Lmx1a pathway.
Department of Pathology and Guangdong Key Laboratory for Bioactive Drugs Research, Guangdong Pharmaceutical University, 510006 Guangzhou, China. Electronic address: janeyuan9909@163.com.
Jian
J
Yuan
Department of Human Anatomy and Neuroscience, Medical School of Southeast University, Dingjiaqiao 87, Nanjing, Jiangsu 210009, China.
Zhi-nian
ZN
Lei
Department of Pathology and Laboratory Medicine, University of Rochester Medical School, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA.
Xi
X
Wang
Department of Pathology, School of Basic Medical Science, Southern Medical University, 510515 Guangzhou, China.
Yong-Jian
YJ
Deng
Department of Pathology and Guangdong Key Laboratory for Bioactive Drugs Research, Guangdong Pharmaceutical University, 510006 Guangzhou, China.
Dong-Bo
DB
Chen
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051559:Hepatocyte Nuclear Factor 6 / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D008636:Mesencephalon / Q000166:cytology* / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D051155:Wnt1 Protein / Q000378:metabolism
D051559:Hepatocyte Nuclear Factor 6; D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C496606:Onecut1 protein, mouse; D014157:Transcription Factors; D051155:Wnt1 Protein
Lmx1a; Oc-1; Parkinson׳s disease; Wnt1; mdDA