The UNC-3 Olf/EBF protein represses alternate neuronal programs to specify chemosensory neuron identity

Kim, Kyuhyung; Colosimo, Marc E.; Yeung, Helen H; Sengupta, Piali

doi:10.1016/j.ydbio.2005.07.024

Cited by 44 publications

(45 citation statements)

References 75 publications

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“…In unc-3(e151) animals, the Y cell is blocked in step 3 of this reprogramming process, supporting the notion that unc-3 activity is needed to complete redifferentiation into a different cell type. UNC-3 has been described as both a transcriptional activator and a repressor (Kim et al, 2005). It is thus revealing that mutations in UNC-3 that destroy the zinc-finger coordination motif in the DNA-binding domain or the integrity of the IPT domain, which is thought to be important for DNA binding, result in the most penetrant Y-to-PDA defects, suggesting that DNA binding is key to UNC-3 activity during Y transdifferentiation.…”

Section: Discussionmentioning

confidence: 99%

Direct in vivo cellular reprogramming involves transition through discrete, non-pluripotent steps

et al. 2011

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SUMMARYCells can change identity during normal development, in response to tissue damage or defined artificial treatments, or during disease processes such as cancer. Strikingly, not only the reprogramming of tissue cells to an embryonic stem cell-like state, but also the direct conversion from one cell type to another have been described. Direct cell type conversion could represent an alternative strategy for cellular therapies. However, little is known about the actual cellular steps undertaken by a cell as it changes its identity and their possible consequences for the organism. Using an in vivo single-cell system of natural direct reprogramming, in which a C. elegans rectal cell transforms into a motoneuron, we present an in-depth analysis of the cellular transformations involved. We found that the reprogrammed cell transits through intermediate states during direct in vivo reprogramming. We identified and characterised a mutant in the conserved COE transcription factor UNC-3 in which this cellular transformation is blocked. We determined that complete erasure of initial identity first takes place, followed by stepwise, unc-3-dependent, redifferentiation into a motoneuron. Furthermore, unlike in vitro induced reprogramming, reversion to a dedifferentiated identity does not lead to an increase in cellular potential in a natural, in vivo context. Our findings suggest that direct cell type conversion occurs via successive steps, and that dedifferentiation can occur in the absence of cell division. Furthermore, our results suggest that mechanisms are in place in vivo to restrict cell potential during reprogramming, a finding with important implications for regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Direct in vivo cellular reprogramming involves transition through discrete, non-pluripotent steps

et al. 2011

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“…UNC-3, the single C. elegans COE family transcription factor, specifies the identity of cholinergic motor neurons and ASI sensory neurons, and promotes postembryonic epithelial to neuron transition in the Y cell (Kim et al, 2005;Prasad et al, 2008;Richard et al, 2011;Kratsios et al, 2012). Here we show that UNC-3, in partner with alternate co-factors, acts as a lineagespecific activator of apoptosis in the RID neuron lineage.…”

Section: Discussionmentioning

confidence: 69%

“…The most significant reduction in rescuing activity occurred when a 1.2 kb 3′ downstream region was removed (Fig. 5B,D (Wang et al, 1993;Kim et al, 2005;Kratsios et al, 2012). Within this 1.2 kb egl-1 fragment, we identified two putative COE binding sites (sites 1 and 2) and a less stringent binding site (site 3), which are conserved among the C. elegans, C. remaneii, C. briggsae and C. brenneri genomes (Fig.…”

Section: Unc-3 Is Expressed and Functionally Required In The Rid Lineagementioning

confidence: 91%

“…UNC-3 is a terminal selector for a fraction of cholinergic motor neurons and sensory neurons (Kim et al, 2005;Kratsios et al, 2012). We first examined whether the RID fate is altered in unc-3 mutants.…”

Section: Unc-3 Is Non-essential For Rid Terminal Differentiationmentioning

confidence: 99%

“…UNC-3 is required for the postmitotic hindgut hypodermal Y cell to redifferentiate into a PDA motor neuron (Richard et al, 2011;Zuryn et al, 2014). UNC-3 promotes the identity of the ASI chemosensory neuron by activating the expression of ASI-specific genes and repressing alternative neuronal programs (Kim et al, 2005). In a fraction of cholinergic motor neurons, UNC-3 functions as the terminal selector for cholinergic fate (Kratsios et al, 2012) and further restricts the identity of the VA and VB subclass cholinergic motor neurons by repressing the VC-type subclass fate (Prasad et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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The C. elegans COE transcription factor UNC-3 activates lineage-specific apoptosis and affects neurite growth in the RID lineage

Wang

Chitturi

et al. 2015

Development

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Mechanisms that regulate apoptosis in a temporal and lineagespecific manner remain poorly understood. The COE (Collier/Olf/ EBF) transcription factors have been implicated in the development of many cell types, including neurons. Here, we show that the sole Caenorhabditis elegans COE protein, UNC-3, together with a histone acetyltransferase, CBP-1/P300, specifies lineage-specific apoptosis and certain aspects of neurite trajectory. During embryogenesis, the RID progenitor cell gives rise to the RID neuron and RID sister cell; the latter undergoes apoptosis shortly after cell division upon expression of the pro-apoptotic gene egl-1. We observe UNC-3 expression in the RID progenitor, and the absence of UNC-3 results in the failure of the RID lineage to express a Pegl-1::GFP reporter and in the survival of the RID sister cell. Lastly, UNC-3 interacts with CBP-1, and cbp-1 mutants exhibit a similar RID phenotype to unc-3. Thus, in addition to playing a role in neuronal terminal differentiation, UNC-3 is a cell lineage-specific regulator of apoptosis.

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Cis‐regulatory mechanisms of gene expression in an olfactory neuron type in Caenorhabditis elegans

Nokes

Linden

Winslow

et al. 2009

Developmental Dynamics

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The generation of cellular diversity is dependent on the precise spatiotemporal regulation of gene expression by both cis- and trans-acting mechanisms. The developmental principles regulating expression of specific gene subsets in individual cell types are not fully understood. Here we define the cis-regulatory mechanisms driving expression of cell-selective and broadly expressed genes in vivo in the AWB olfactory neuron subtype in C. elegans. We identify an element that is necessary to drive expression of neuron-selective chemoreceptor genes in the AWB neurons, and show that this element functions in a context-dependent manner. We find that the expression of broadly expressed sensory neuronal genes in the AWB neurons is regulated by diverse cis- and trans-regulatory mechanisms that act partly in parallel to the pathways governing expression of AWB-selective genes. We further demonstrate that cis-acting mechanisms driving gene expression in the AWB neurons appear to have diverged in related nematode species. Our results provide insights into the cis-regulatory logic driving cell-specific gene expression, and suggest that variations in this logic contribute to the generation of functional diversity.

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The UNC-3 Olf/EBF protein represses alternate neuronal programs to specify chemosensory neuron identity

Cited by 44 publications

References 75 publications

Direct in vivo cellular reprogramming involves transition through discrete, non-pluripotent steps

Direct in vivo cellular reprogramming involves transition through discrete, non-pluripotent steps

The C. elegans COE transcription factor UNC-3 activates lineage-specific apoptosis and affects neurite growth in the RID lineage

Cis‐regulatory mechanisms of gene expression in an olfactory neuron type in Caenorhabditis elegans

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