title: Embryonic priming of a miRNA locus predetermines postmitotic neuronal left/right asymmetry in C. elegans.
abstract: The mechanisms by which functional left/right asymmetry arises in morphologically symmetric nervous systems are poorly understood. Here, we provide a mechanistic framework for how functional asymmetry in a postmitotic neuron pair is specified in C. elegans. A key feature of this mechanism is a temporally separated, two-step activation of the lsy-6 miRNA locus. The lsy-6 locus is first "primed" by chromatin decompaction in the precursor for the left neuron, but not the right neuron, several divisions before the neurons are born. lsy-6 expression is then "boosted" to functionally relevant levels several divisions later in the mother of the left neuron, through the activity of a bilaterally expressed transcription factor that can only activate lsy-6 in the primed neuron. This study shows how cells can become committed during early developmental stages to execute a specific fate much later in development and provides a conceptual framework for understanding the generation of neuronal diversity.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University Medical Center, New York, NY 10032, USA. mlc2155@columbia.edu
authors.forename: Luisa
authors.initials: L
authors.lastname: Cochella
authors.forename: Oliver
authors.initials: O
authors.lastname: Hobert
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D019070:Cell Lineage; D004625:Embryo, Nonmammalian / Q000378:metabolism; D015870:Gene Expression; D035683:MicroRNAs / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: C578012:MIRNLsy-6 microRNA, C elegans; D035683:MicroRNAs; D051880:Receptors, Notch