title: Timing mechanisms in neuronal pathfinding, synaptic reorganization, and neuronal regeneration.
abstract: Precise temporal control of neuro differentiation and post-differentiation events are necessary for the creation of appropriate wiring diagram in the brain. To make advances in the treatment of neurodevelopmental and neurodegenerative disorders, and traumatic brain injury, it is important to understand these mechanisms. Caenorhabditis elegans has emerged as a revolutionary tool for the study of neural circuits due to its genetic homology to vertebrates and ease of genetic manipulation. microRNA (miRNA), a ubiquitous class of small non-coding RNA, that inhibits the expression of target genes, has emerged as an important timing control molecule through research conducted on C. elegans. This review will focus on the temporal control of neurodifferentiation and post-differentiation events exerted by two conserved miRNAs, lin-4 and let-7. We summarize recent findings on the role of lin-4 as a timing regulator controlling transition of sequential events in neuronal pathfinding and synaptic remodeling, and the role of let-7 as a timing regulator that limits the regeneration potential of post-differentiated AVM neurons as they age.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, 60607, USA.|Medical Scientist Training Program, University of Illinois at Chicago, Chicago, IL, 60612, USA.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Ivakhnitskaia
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, 60607, USA.|Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL, 60612, USA.
authors.forename: Kana
authors.initials: K
authors.lastname: Hamada
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, 60607, USA.|Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL, 60612, USA.
authors.forename: Chieh
authors.initials: C
authors.lastname: Chang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C474488:let-7 microRNA, C elegans; C452194:lin-4 microRNA, C elegans
keywords: neuronal connectivity; neuronal pathfinding; neuronal regeneration; synapse formation; timing mechanisms