UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans

Winnier, Angela R.; Meir, James Y.; Ross, Jen; Tavernarakis, Nektarios; Driscoll, Monica; Ishihara, Takeshi; Izui, Katsura; Miller, David M.

doi:10.1101/gad.13.21.2774

Cited by 117 publications

(164 citation statements)

References 54 publications

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…We identified a C . T mutation at 9,897,945 (ws200) in a splice-acceptor site in the unc-4 gene as e120, consistent with its original molecular description (Winnier et al 1999). In rol-1, the causal mutation underlying e91 has not been described.…”

Section: Strainsmentioning

confidence: 51%

Crossover Heterogeneity in the Absence of Hotspots inCaenorhabditis elegans

Kaur

Rockman

2014

Genetics

View full text Add to dashboard Cite

Crossovers play mechanical roles in meiotic chromosome segregation, generate genetic diversity by producing new allelic combinations, and facilitate evolution by decoupling linked alleles. In almost every species studied to date, crossover distributions are dramatically nonuniform, differing among sexes and across genomes, with spatial variation in crossover rates on scales from whole chromosomes to subkilobase hotspots. To understand the regulatory forces dictating these heterogeneous distributions a crucial first step is the fine-scale characterization of crossover distributions. Here we define the wild-type distribution of crossovers along a region of the C. elegans chromosome II at unprecedented resolution, using recombinant chromosomes of 243 hermaphrodites and 226 males. We find that well-characterized large-scale domains, with little fine-scale rate heterogeneity, dominate this region's crossover landscape. Using the Gini coefficient as a summary statistic, we find that this region of the C. elegans genome has the least heterogeneous fine-scale crossover distribution yet observed among model organisms, and we show by simulation that the data are incompatible with a mammalian-type hotspot-rich landscape. The large-scale structural domains-the low-recombination center and the high-recombination arm-have a discrete boundary that we localize to a small region. This boundary coincides with the armcenter boundary defined both by nuclear-envelope attachment of DNA in somatic cells and GC content, consistent with proposals that these features of chromosome organization may be mechanical causes and evolutionary consequences of crossover recombination. MEIOTIC recombination creates novel combinations of parental alleles and is a powerful force shaping the genetic variation observed within a population. The frequency of recombination has a profound impact on the efficacy of natural selection in both purging deleterious mutations and in the formation of beneficial allelic combinations (Hill and Robertson 1966;Cutter and Payseur 2013). However, the intensity of recombination in different parts of a genome is rarely constant. Heterogeneity in the meiotic recombination rate has been observed across chromosome lengths and at finer scales of a few kilobase in diverse organisms.In Caenorhabditis elegans, meiotic recombination rates show a striking and reproducible chromosome-wide pattern of variation. Genetic maps of the five autosomes and X chromosome show that each has a low-recombination central domain flanked by high-recombination arm domains (Barnes et al. 1995;Rockman and Kruglyak 2009). This domain structure has dramatic effects on genetic variation and evolution (Cutter and Payseur 2003;Rockman et al. 2010;Andersen et al. 2012), but the underlying causes generating this pattern are not completely understood.The domain structure relates to unusual characteristics of the C. elegans chromosomes. The chromosomes lack localized centromeres and exhibit holocentric segregation during mitosis, with kinetochore pro...

show abstract

Section: Strainsmentioning

confidence: 51%

Crossover Heterogeneity in the Absence of Hotspots inCaenorhabditis elegans

Kaur

Rockman

2014

Genetics

View full text Add to dashboard Cite

show abstract

“…It is interesting that both ceh-30 and unc-37 are widely expressed in C. elegans embryos ( Fig. 4A; Winnier et al 1999), yet ceh-30 specifically represses cell death only in male CEMs. This observation and the finding that the CEH-30 homeodomain is largely dispensable for its death inhibitory activity in CEMs suggest that CEH-30 may act to bridge the repressosome formation of UNC-37/Groucho with a CEM-specific transcription factor that directs repressosome binding to the promoter of a critical proapoptotic target gene and thus represses CEM cell death in males (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…We then examined animals defective in the unc-37 gene, which encodes the C. elegans Groucho ortholog (Pflugrad et al 1997;Winnier et al 1999), to determine if unc-37 is involved in CEM cell fate specification. Male animals carrying the only viable allele of unc-37(e262) showed decreased CEM survival (Table 4), whereas the unc-37(e262); ced-3(n2433) double mutant showed normal CEM survival in male animals.…”

Section: The N-terminal Eh1/fil Motif Of Ceh-30 and Unc-37/groucho Armentioning

confidence: 99%

Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho

Peden¹,

Kimberly²,

Gengyo-Ando³

et al. 2007

Genes Dev.

View full text Add to dashboard Cite

Apoptosis is essential for proper development and tissue homeostasis in metazoans. It plays a critical role in generating sexual dimorphism by eliminating structures that are not needed in a specific sex. The molecular mechanisms that regulate sexually dimorphic apoptosis are poorly understood. Here we report the identification of the ceh-30 gene as a key regulator of sex-specific apoptosis in Caenorhabditis elegans. Loss-of-function mutations in ceh-30 cause the ectopic death of male-specific CEM neurons. ceh-30 encodes a BarH homeodomain protein that acts downstream from the terminal sex determination gene tra-1, but upstream of, or in parallel to, the cell-death-initiating gene egl-1 to protect CEM neurons from undergoing apoptosis in males. The second intron of the ceh-30 gene contains two adjacent cis-elements that are binding sites for TRA-1A and a POU-type homeodomain protein UNC-86 and acts as a sensor to regulate proper specification of the CEM cell fate. Surprisingly, the N terminus of CEH-30 but not its homeodomain is critical for CEH-30's cell death inhibitory activity in CEMs and contains a conserved eh1/FIL domain that is important for the recruitment of the general transcriptional repressor UNC-37/Groucho. Our study suggests that ceh-30 defines a critical checkpoint that integrates the sex determination signal TRA-1 and the cell fate determination and survival signal UNC-86 to control the sex-specific activation of the cell death program in CEMs through the general transcription repressor UNC-37.[Keywords: C. elegans; apoptosis; sex-specific; unc-37/Groucho; ceh-30; transcriptional regulation] Supplemental material is available at http://www.genesdev.org.

show abstract

“…Changes in cell fate that are seemingly without consequence during early development have been reported to alter axon projections, while leaving many other aspects of the cell intact (Sharma et al 1998, Thor et al 1999, Sharma & Peng 2001. In this manner, coordinated expression of transcriptional activators and repressors defines neuronal connectivity (Winnier et al 1999, Kania et al 2000. Factors required for defining the connectivity and neuropeptide identity of the HNS during later stages of differentiation have not been identified yet.…”

Section: Introductionmentioning

confidence: 99%

Neurohypophysial dysmorphogenesis in mice lacking the homeobox gene Uncx4•1

Asbreuk

Doorninck²,

Mansouri

et al. 2006

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

A number of transcription factors have been implicated in the development of the hypothalamo-neurohypophysial system (HNS). Null mutations for these factors caused severe defects in proliferation, migration and survival during early embryogenesis. While they have informed about early events of HNS developments no insights in mechanisms of late development and maturation of this major peptidergic system have been obtained as yet. In a screen for adult-expressed homeobox genes we identified Uncx4·1 as a gene expressed in adult and embryonic magnocellular neurons of the (HNS). Null mutation of Uncx4·1 left these neurons viable and able to express neuropeptides. However, the connectivity of magnocellular neurons with posterior pituitary elements was compromised. As a consequence neuronal fibres traversed to the adenohypophysis. The penetrance of this phenotype was about 50%. The data show a selective role of Uncx4·1 in controlling the development of connections of hypothalamic neurons to pituitary elements, allowing central neurons to reach the peripheral blood circulation and to deliver hormones for control of peripheral functions.

show abstract

UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans

Cited by 117 publications

References 54 publications

Crossover Heterogeneity in the Absence of Hotspots inCaenorhabditis elegans

Crossover Heterogeneity in the Absence of Hotspots inCaenorhabditis elegans

Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho

Neurohypophysial dysmorphogenesis in mice lacking the homeobox gene Uncx4•1

Contact Info

Product

Resources

About