Journal
ENEURO
Volume 4, Issue 2, Pages -Publisher
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0349-16.2017
Keywords
Isl1; Isl1-Lhx3; Lhx3; LMO4
Categories
Funding
- NIH/NINDS [R01 NS054941]
- NIH/NIDDK [R01 DK064678, R01 DK103661]
- American Heart Association
- Basic Science Research Program - Korean government (MSIP) through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and future Planning [NRF-2015R1A2A1A15055611]
- Bio AMP
- Medical Technology Development Program - Korean government (MSIP) through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and future Planning [NRF-2012M3A9C6050508]
- Global Core Research Center - Korean government (MSIP) through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and future Planning [2011-0030001]
- Predoctoral Ruth L. Kirstein National Research Service Award (NRSA) from NIH/NINDS [1F31NS084636]
- Portland ARCS Chapter
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available