The Isl1-Lhx3 Complex Promotes Motor Neuron Specification by Activating Transcriptional Pathways that Enhance Its Own Expression and Formation
Year: 2017
Type: article
Abstract: Motor neuron (MN) progenitor cells rapidly induce high expression of the transcription factors Islet-1 (Isl1), LIM-homeobox 3 (Lhx3), and the transcriptional regulator LMO4, as they differentiate. While these factors are critical for MN specification, the mechanisms regulating their precise temporal and spatial expression patterns are not well characterized. Isl1 and Lhx3 form the Isl1-Lhx3 complex, which induces the transcription of genes critical for MN specification and maturation. Here, we report that Isl1 , Lhx3 , and Lmo4 are direct target genes of the Isl1-Lhx3 complex. Our results show that specific genomic loci associated with these genes recruit the Isl1-Lhx3 complex to activate the transcription of Isl1 , Lhx3 , and Lmo4 in embryonic MNs of chick and mouse. These findings support a model in which the Isl1-Lhx3 complex amplifies its own expression through a potent autoregulatory feedback loop and simultaneously enhances the transcription of Lmo4 . LMO4 blocks the formation of the V2 interneuron-specifying Lhx3 complex. In developing MNs, this action inhibits the expression of V2 interneuron genes and increases the pool of unbound Lhx3 available to incorporate into the Isl1-Lhx3 complex. Identifying the pathways that regulate the expression of these key factors provides important insights into the genetic strategies utilized to promote MN differentiation and maturation.
Source: eNeuro
Authors: Madalynn Erb, Bora Lee, So Yeon Seo, Jae W. Lee, Seunghee Lee, Soo-Kyung Lee
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,925
Funders: American Heart Association, National Research Foundation, Ministry of Science, ICT and Future Planning, National Research Foundation of Korea, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W2603329788