A Tale of Tailless

Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, N.J., USA.
Developmental Neuroscience (Impact Factor: 2.7). 12/2010; 33(1):1-13. DOI: 10.1159/000321585
Source: PubMed


Drosophila Tailless(Tll) and its vertebrate homologue Tlx are conserved orphan nuclear receptors specifically expressed in the eye and the forebrain. Tll and Tlx act primarily as transcriptional repressors through their interactions with transcriptional corepressors, Atrophin family proteins, and histone-tail/chromatin-modifying factors such as lysine-specific histone demethylase 1 and histone deacetylases. The functional importance of Tll and Tlx is made apparent by the recent discovery that they are expressed in neural stem cells (NSCs) and are required for self-renewal of these cells in both Drosophila and the mouse. This review provides a snapshot of current knowledge about Tll and Tlx and their transcriptional network, which maintains NSCs in developing and adult animals.

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    • "To identify the target gene in DAGL/inaE EP1101 responsible for lifespan extension and stress resistance, we performed a plasmid rescue and verified that a single EP-element insertion was present in the 5 0 un-translated region of DAGL/inaE. The EP-element insertion in DAGL/ inaE EP1101 disrupts the binding site of a transcriptional repressor Tailless (Gui et al., 2011). Semi-quantitative RT-PCR analysis revealed a threefold increase of DAGL/inaE mRNA levels in DAGL/inaE EP1101 compared with the control (Fig. 1C). "
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    ABSTRACT: Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unknown. DAG is metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn-glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl-1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S6K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging.
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    • "TLX is an important regulator of stem cell fate in forebrain and retina (45), and defects in its expression are associated with behavioural abnormalities, blindness and glioblastoma as reviewed in (46). In addition to its role in development, TLX expression has been detected in neural stem cells in adult brain within cells lining the subventricular zone, and the subgranular layer of the dentate gyrus, as well as in striatum and cortex (47). "
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    ABSTRACT: Despite their physiological importance, selective interactions between nuclear receptors (NRs) and their cofactors are poorly understood. Here, we describe a novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitates its selective interaction with members of the NR2E/F subfamily. Two copies of this motif (named here as RID1 and RID2) permit BCL11A to bind COUP-TFs (NR2F1;NR2F2;NR2F6) and Tailless/TLX (NR2E1), whereas RID1, but not RID2, binds PNR (NR2E3). We confirmed the existence of endogenous BCL11A/TLX complexes in mouse cortex tissue. No interactions of RID1 and RID2 with 20 other ligand-binding domains from different NR subtypes were observed. We show that RID1 and RID2 are required for BCL11A-mediated repression of endogenous γ-globin gene and the regulatory non-coding transcript Bgl3, and we identify COUP-TFII binding sites within the Bgl3 locus. In addition to their importance for BCL11A function, we show that F/YSXXLXXL/Y motifs are conserved in other NR cofactors. A single FSXXLXXL motif in the NR-binding SET domain protein NSD1 facilitates its interactions with the NR2E/F subfamily. However, the NSD1 motif incorporates features of both LXXLL and FSXXLXXL motifs, giving it a distinct NR-binding pattern in contrast to other cofactors. In summary, our results provide new insights into the selectivity of NR/cofactor complex formation.
    Full-text · Article · Aug 2013 · Nucleic Acids Research
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    • "In the anterior region, tll is also detected at later blastoderm stages. In Drosophila and in other arthropods, this tll expression is correlated to neurogenic roles (Gui et al., 2011). "
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