Dataset Information

Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.

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.

SUBMITTER: Kim N

PROVIDER: S-EPMC4598079 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.

Kim Namhee N Park Chungoo C Jeong Yongsu Y Song Mi-Ryoung MR

PLoS genetics 20151008 10

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 co ...[more]

PMID: 26447474

Similar Datasets

Project description:The motor neuron (MN)–hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN–hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN–hexamer–bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN–hexamer, enhancing the transcriptional activity of the MN–hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN–hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord. To explain our experimental scheme briefly, we are interested in finding target sites for the dimer of transcription factors Isl1 and Lhx3. To mimic the biological activity of Isl1/Lhx3 dimer, we made Isl1-Lhx3 fusion and found that Isl1-Lhx3 has a potent biological activity in multiple systems (i.e. generation of ectopic motor neurons). Then we made ES cell line that induces Flag-tagged Isl1-Lhx3 expression upon Dox treatment. These *mouse* ES cells differentiate to motor neurons (iMN-ESCs) when treated with Dox following EB formation. To identify genomic binding sites of Isl1-Lhx3 (Flag-tagged), we performed ChIP with Flag antibody (pull down of Flag-Isl1-Lhx3) in ES cells treated with Dox. ChIP with Flag antibody in ES cells treated with vehicle (no Dox) was done as a negative control in parallel, and sequenced along with +Dox sample. We have done these experiments twice (two sets).

Dataset Information

Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.

Publications

Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets