title: Cell fate determination, neuronal maintenance and disease state: The emerging role of transcription factors Lmx1a and Lmx1b.
abstract: LIM-homeodomain (LIM-HD) proteins are evolutionary conserved developmental transcription factors. LIM-HD Lmx1a and Lmx1b orchestrate complex temporal and spatial gene expression of the dopaminergic pathway, and evidence shows they are also involved in adult neuronal homeostasis. In this review, the multiple roles played by Lmx1a and Lmx1b will be discussed. Controlled Lmx1a and Lmx1b expression and activities ensure the proper formation of critical signaling centers, including the embryonic ventral mesencephalon floor plate and sharp boundaries between lineage-specific cells. Lmx1a and Lmx1b expression persists in mature dopaminergic neurons of the substantia nigra pars compacta and the ventral tegmental area, and their role in the adult brain is beginning to be revealed. Notably, LMX1B expression was lower in brain tissue affected by Parkinson's disease. Actual and future applications of Lmx1a and Lmx1b transcription factors in stem cell production as well as in direct conversion of fibroblast into dopaminergic neurons are also discussed. A thorough understanding of the role of LMX1A and LMX1B in a number of disease states, including developmental diseases, cancer and neurodegenerative diseases, could lead to significant benefits for human healthcare.
authors.affiliation: Department of Psychiatry and Neurosciences, Faculty of Medicine, Université Laval, Québec, QC, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, 2601, chemin de la Canardière, Québec, QC G1J 2G3, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Doucet-Beaupré
authors.affiliation: Division of Developmental Neurobiology, MRC-National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Siew-Lan
authors.initials: SL
authors.lastname: Ang
authors.affiliation: Department of Psychiatry and Neurosciences, Faculty of Medicine, Université Laval, Québec, QC, Canada; Centre de recherche de l'Institut universitaire en santé mentale de Québec, 2601, chemin de la Canardière, Québec, QC G1J 2G3, Canada. Electronic address: martin.levesque@fmed.ulaval.ca.
authors.forename: Martin
authors.initials: M
authors.lastname: Lévesque
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000502:physiology*; D055495:Neurogenesis; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; D014157:Transcription Factors
keywords: Cancer; Neurodegeneration; Parkinson’s disease; Stem cell