ArticlePLoS genetics2015
Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Genetic knockout suggests Isl1 enhancer redundancy in mouse hindlimb development.Developmental biology · 2025Article
- A modular enhancer mediates SCRT2 repression of ISLET1 in the spinal cord.Developmental biology · 2025Article
- An integrated transcriptomic approach for identifying enhancers in limb motor pools.Scientific reports · 2025Article
- CUT homeobox genes: transcriptional regulation of neuronal specification and beyond.Frontiers in cellular neuroscience · 2023Review
- Review
- An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity.Neuron · 2022Article
- Deleterious Variation in BR Serine/Threonine Kinase 2 Classified a Subtype of Autism.Frontiers in molecular neuroscience · 2022Article
- Onecut Regulates Core Components of the Molecular Machinery for Neurotransmission in Photoreceptor Differentiation.Frontiers in cell and developmental biology · 2021Article
- A Highly ConservedFrontiers in cell and developmental biology · 2021Article
- Standardized Reporter Systems for Purification and Imaging of Human Pluripotent Stem Cell-derived Motor Neurons and Other Cholinergic Cells.Neuroscience · 2020Article
- AdultFrontiers in neuroanatomy · 2019Article
- Gata6 restricts Isl1 to the posterior of nascent hindlimb buds through Isl1 cis-regulatory modules.Developmental biology · 2018Article
- Role of the LF-SINE-Derived DistalJournal of pediatric genetics · 2017Article
- JAK-STAT pathway activation in response to spinal cord injury in regenerative and non-regenerative stages ofRegeneration (Oxford, England) · 2017Article
- The Onecut Transcription Factors Regulate Differentiation and Distribution of Dorsal Interneurons during Spinal Cord Development.Frontiers in molecular neuroscience · 2017Article
- An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons.Genes & development · 2016Article
- ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons.Scientific reports · 2016Article
- Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Functional diversification of motor neurons has occurred in order to selectively control the movements of different body parts including head, trunk and limbs. Here we report that transcription of Isl1, a major gene necessary for motor neuron identity, is controlled by two enhancers, CREST1 (E1) and CREST2 (E2) that allow selective gene expression of Isl1 in motor neurons. Introduction of GFP reporters into the chick neural tube revealed that E1 is active in hindbrain motor neurons and spinal cord motor neurons, whereas E2 is active in the lateral motor column (LMC) of the spinal cord, which controls the limb muscles. Genome-wide ChIP-Seq analysis combined with reporter assays showed that Phox2 and the Isl1-Lhx3 complex bind to E1 and drive hindbrain and spinal cord-specific expression of Isl1, respectively. Interestingly, Lhx3 alone was sufficient to activate E1, and this may contribute to the initiation of Isl1 expression when progenitors have just developed into motor neurons. E2 was induced by onecut 1 (OC-1) factor that permits Isl1 expression in LMCm neurons. Interestingly, the core region of E1 has been conserved in evolution, even in the lamprey, a jawless vertebrate with primitive motor neurons. All E1 sequences from lamprey to mouse responded equally well to Phox2a and the Isl1-Lhx3 complex. Conversely, E2, the enhancer for limb-innervating motor neurons, was only found in tetrapod animals. This suggests that evolutionarily-conserved enhancers permit the diversification of motor neurons.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.