A Regulatory Network to Segregate the Identity of Neuronal Subtypes

Lee, Seung‐Hee; Lee, Bora; Joshi, Kaumudi; Pfaff, Samuel L.; Lee, Soo Kyung

doi:10.1016/j.devcel.2008.03.021

Cited by 103 publications

(102 citation statements)

References 54 publications

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“…Although LMO proteins have no DNAbinding activity, a strong interaction between LMO and the nuclear LIM interactor (NLI/LDB1/CLIM2) was predicted to be responsible for negatively regulating transcription by inhibiting NLI from forming complexes with LIM-HD factors. This prediction was supported by studies in Drosophila and the vertebrate spinal cord (Milán et al, 1998;Lee et al, 2008;Joshi et al, 2009;Song et al, 2009). However, LMO4 and its binding partner NLI have been shown to interact with the basichelix-loop-helix protein Neurogenin 2 (NGN2) to form a multiprotein transcription complex, which is recruited to the E-box containing enhancers of NGN2-target genes to activate transcription (Asprer et al, 2011).…”

Section: Lmo4 Is a Transcriptional Modulatorsupporting

confidence: 52%

“…LMO4 belongs to a protein subfamily encoded by four genes (LMO1-4 ), and its paralogues LMO1 and LMO3 are NB oncogenes (Aoyama et al, 2005;Isogai et al, 2011;Wang et al, 2011). In the developing mammalian spinal cord, LMO4 contributes to the segregation of neuronal subtypes Joshi et al, 2009) and, in the Xenopus embryo, participates in the acquisition of NC identity (Ochoa et al, 2012). Here, we show that LMO4 is expressed in human NB cells and chick NC cells.…”

Section: Introductionmentioning

confidence: 76%

“…The BMP reporter construct (BRE-tk-GFP) used here has been previously described (Le Dréau et al, 2012), as has the E-cadherin-luciferase reporter construct (Batlle et al, 2000). Human LMO4 (Lu et al, 2006) and chicken Snail2 (Morales et al, 2007) were subcloned into pCAGGS-ires-GFP or pCAGGS-ires-H2B-RFP.…”

Section: Methodsmentioning

confidence: 99%

“…We identified LMO4 in a genome-wide screening based on a BMP-reporter and found that LMO4 was sufficient to activate the BRE-tk-GFP reporter in the NT (data not shown). As Smad1/5 (Le Dréau et al, 2012) and Smad3 (García-Campmany and Marti, 2007) are expressed in the developing NT, we propose a model in which LMO4 enhances the transcriptional activity of endogenous Smad1/5 proteins to activate BMP-dependent responses.…”

Section: Lmo4 Is a Transcriptional Modulatormentioning

confidence: 99%

“…1A) (Le Dréau et al, 2012). Chick embryos [Hamilton-Hamburger (HH) stage 10] were coelectroporated with BRE-tk-GFP and pCAGGS-ires-H2B-RFP, which drives RFP expression along the entire dorsal-ventral axis of the NT.…”

Section: Lmo4 Is Common To Neural Crest and Neuroblastoma Cellsmentioning

confidence: 99%

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LMO4 is an Essential Cofactor in the Snail2-Mediated Epithelial-to-Mesenchymal Transition of Neuroblastoma and Neural Crest Cells

et al. 2013

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Neuroblastoma is an embryonic tumor derived from cells of the neural crest. Taking advantage of a newly developed neural crest lineage tracer and based on the hypothesis that the molecular mechanisms that mediate neural crest delamination are also likely to be involved in the spread of neuroblastoma, we were able to identify genes that are active both in neural crest development and neuroblastoma tumor formation. A subsequent search of the neuroblastoma gene server for human orthologues of genes differentially expressed in the chick embryo neural crest screen retrieved the LIM domain only protein 4 (LMO4), which was expressed in both cell types analyzed. Functional experiments in these two model systems revealed that LMO4 activity is required for neuroblastoma cell invasion and neural crest delamination. Moreover, we identified LMO4 as an essential cofactor in Snail2-mediated cadherin repression and in the epithelial-tomesenchymal transition of both neural crest and neuroblastoma cells. Together, our results suggest that the association of high levels of LMO4 with aggressive neuroblastomas is dependent on LMO4 regulation of cadherin expression and hence, tumor invasiveness.

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Section: Lmo4 Is a Transcriptional Modulatorsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Section: Lmo4 Is a Transcriptional Modulatormentioning

confidence: 99%

Section: Lmo4 Is Common To Neural Crest and Neuroblastoma Cellsmentioning

confidence: 99%

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LMO4 is an Essential Cofactor in the Snail2-Mediated Epithelial-to-Mesenchymal Transition of Neuroblastoma and Neural Crest Cells

et al. 2013

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Regulation of Neuronal Subtype Identity in the Vertebrate Neural Tube (Neuronal Subtype Identity Regulation)

Bushati¹,

Briscoe²

2012

Encyclopedia of Life Sciences

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The vertebrate nervous system consists of many different neuronal cell types. Each has its own properties, axon projections and connection patterns. This diversity is established early during development and is required for the complex neuronal circuits that characterise the central nervous system. In the spinal cord, a series of events generates different neuronal subtypes, starting with the spatial patterning of neural progenitors. Extrinsic signals provide progenitors in the forming neural tube with positional identity, such that distinct types of progenitors express a unique combination of transcription factors. This transcriptional code determines neural progenitor identity. As progenitors differentiate, they generate distinct neuronal subtypes that are also characterised by a combinatorial transcriptional code. In addition to spatial patterning, other mechanisms contribute to the further diversification of differentiating neurons. Key Concepts: Secreted molecules provide positional information to neural progenitors in the developing neural tube. Progenitors at different positions in the neural tube acquire distinct identities. The identity of a progenitor is defined by the combination of transcription factors it expresses, which determines the gene expression profile of the progenitor. An interplay between extrinsic signalling and the downstream gene network produces spatially discrete switches in progenitor identity. Progenitors with distinct identities differentiate into post‐mitotic neurons with different subtype identities. The identity of a neuron is determined by the transcriptional code of its progenitor and is itself defined by a separate transcriptional code. In addition to spatial pattern, temporal changes in progenitor identity and signalling between differentiating cells increases neuronal diversity.

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A Quantitative Fluorescence‐Based Assay for Assessing LIM Domain–Peptide Interactions

2016

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We have developed Fçrster resonance energy transfer (FRET)-based experiments for measuring the binding affinity,o ff-rates,a nd inferred on-rates for interactions between af amily of transcriptional regulators and their intrinsically disordered binding partners.I tw as difficult to evaluate these interactions previously,a st he transcriptional regulators are obligate binding proteins that aggregate in the absence of ab inding partner.T he assays rely on fusion constructs where binding domains are linked by af lexible tether containing as pecific protease site,w ith fluorescent proteins at either end that displayF RET when the complex is formed. Loss of FRET is monitored after cutting the tether followed by dilution or competition with an on-fluorescent peptide.T hese methods allowed aw ide range of binding affinities (10 À9 -10 À5 m)t o be determined. Our data indicate that interactions of closely related proteins can have surprisingly different binding properties.

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A Regulatory Network to Segregate the Identity of Neuronal Subtypes

Cited by 103 publications

References 54 publications

LMO4 is an Essential Cofactor in the Snail2-Mediated Epithelial-to-Mesenchymal Transition of Neuroblastoma and Neural Crest Cells

LMO4 is an Essential Cofactor in the Snail2-Mediated Epithelial-to-Mesenchymal Transition of Neuroblastoma and Neural Crest Cells

Regulation of Neuronal Subtype Identity in the Vertebrate Neural Tube (Neuronal Subtype Identity Regulation)

A Quantitative Fluorescence‐Based Assay for Assessing LIM Domain–Peptide Interactions

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