The Ftz‐F1 family: Orphan nuclear receptors regulated by novel protein–protein interactions

Pick, Leslie; Anderson, W. Ray; Shultz, Jeffrey W.; Woodard, Craig T.

doi:10.1016/s1574-3349(06)16008-1

Cited by 17 publications

(19 citation statements)

References 210 publications

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“…Like other NRs, the Ftz-F1/SF-1 family proteins physically interact with transcriptional coactivators and DNA-binding transcription factors (Pick et al, 2006). In C. elegans , direct physical and genetic interactions have been reported between NHR-25 and two Hox proteins, LIN-39 and NOB-1.…”

Section: Discussionmentioning

confidence: 99%

“…In the gonadal precursor cells, the physical interaction between NHR-25 and C. elegans β-catenins, WRM-1 and SYS-1, is important to modulate the Wnt/β-catenin signaling (Asahina et al, 2006). Because the specific interaction between Ftz-F1/SF-1 and the binding partners may explain the spatial- and/or temporal-specific function of Ftz-F1/SF-1 (Pick et al, 2006), NHR-25 may have a certain binding partner that directs gene expression by itself and/or modulates the protein subcellular localizations for each adult differentiation program. Identifying potential binding partners for NHR-25 in seam cells would shed light on how NHR-25 has a variety of roles among different adult differentiation programs.…”

Section: Discussionmentioning

confidence: 99%

“…Alternate segments are deleted in ftz-f1 mutant embryos in a pair-rule fashion, as they are in mutants for the homeodomain protein Fushi tarazu (Ftz), with which Ftz-F1 interacts (Pick et al, 2006). Previous studies have indicated that spatial embryonic patterning in Drosophila segmentation and temporal patterning in seam cells of C. elegans share key conserved genes.…”

Section: Discussionmentioning

confidence: 99%

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The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition

Hada

Asahina

Hasegawa

et al. 2010

Developmental Biology

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Developmental timing in the nematode Caenorhabditis elegans is controlled by heterochronic genes, mutations in which cause changes in the relative timing of developmental events. One of the heterochronic genes, let-7, encodes a microRNA that is highly evolutionarily conserved, suggesting that similar genetic pathways control developmental timing across phyla. Here we report that the nuclear receptor nhr-25, which belongs to the evolutionarily conserved fushi tarazu-factor 1/nuclear receptor NR5A subfamily, interacts with heterochronic genes that regulate the larva-to-adult transition in C. elegans. We identified nhr-25 as a regulator of apl-1, a homolog of the Alzheimer’s amyloid precursor protein-like gene that is downstream of let-7 family microRNAs. NHR-25 controls not only apl-1 expression but also regulates developmental progression in the larva-to-adult transition. NHR-25 negatively regulates the expression of the adult-specific collagen gene col-19 in lateral epidermal seam cells. In contrast, NHR-25 positively regulates the larva-to-adult transition for other timed events in seam cells, such as cell fusion, cell division and alae formation. The genetic relationships between nhr-25 and other heterochronic genes are strikingly varied among several adult developmental events. We propose that nhr-25 has multiple roles in both promoting and inhibiting the C. elegans heterochronic gene pathway controlling adult differentiation programs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition

Hada

Asahina

Hasegawa

et al. 2010

Developmental Biology

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“…The ftz mutant was ftz 9H34 balanced over TM3, hb-lacZ to identify mutant embryos. Embryos derived from ftz-f1 germline clones (referred to as ftz-f1 mutants) were generated with the autosomal FLP-DFS technique (Chou and Perrimon, 1992; Chou and Perrimon, 1996; Chou et al, 1993) using ftz-f1 19 (Broadus et al, 1999; Fortier et al, 2003; Pick et al, 2006). Ftz was ectopically expressed throughout blastoderm embryos by mating UAS-myc-ftz males (Lohr and Pick, 2005) with females homozygous for an NGT40/GAL4 driver (Tracey et al, 2000).…”

Section: Methodsmentioning

confidence: 99%

“…However, like other Hox proteins, Ftz binding to DNA is weak and promiscuous, with >14 million predicted binding sites in the Drosophila genome (Bowler et al, 2006). The specificity of Ftz target site selection is achieved by Ftz interaction with a specific cofactor, the orphan nuclear receptor Ftz-F1, whose DNA binding specificity is much more stringent than that of Ftz (Florence et al, 1997; Guichet et al, 1997; Yu et al, 1997); reviewed in (Pick et al, 2006). Ftz and Ftz-F1 form a stable complex in vivo and bind cooperatively to DNA (Yu et al, 1997; Yussa et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Stripy Ftz target genes are coordinately regulated by Ftz-F1

Hou

Heffer

Anderson

et al. 2009

Developmental Biology

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During development, cascades of regulatory genes act in a hierarchical fashion to subdivide the embryo into increasingly specified body regions. This has been best characterized in Drosophila, where genes encoding regulatory transcription factors form a network to direct the development of the basic segmented body plan. The pair-rule genes are pivotal in this process as they are responsible for the first subdivision of the embryo into repeated metameric units. The Drosophila pair-rule gene fushi tarazu (ftz) is a derived Hox gene expressed in and required for the development of alternate parasegments. Previous studies suggested that Ftz achieves its distinct regulatory specificity as a segmentation protein by interacting with a ubiquitously expressed cofactor, the nuclear receptor Ftz-F1. However, the downstream target genes regulated by Ftz and other pair-rule genes to direct segment formation are not known. In this study, we selected candidate Ftz targets by virtue of their early expression in Ftz-like stripes. This identified two new Ftz target genes, drumstick (drm) and no ocelli (noc), and confirmed that Ftz regulates a serotonin receptor (5-HT2). These are the earliest Ftz targets identified to date and all are coordinately regulated by Ftz-F1. Engrailed (En), the best-characterized Ftz/Ftz-F1 downstream target, is not an intermediate in regulation. The drm genomic region harbors two separate 7-stripe enhancers, identified by virtue of predicted Ftz-F1 binding sites and these sites are necessary for stripe expression in vivo. We propose that pair-rule genes, exemplified by Ftz/Ftz-F1, promote segmentation by acting at different hierarchical levels, regulating first, other segmentation genes; second, other regulatory genes that in turn control specific cellular processes such as tissue differentiation; and, third, 'segmentation realizator genes' that are directly involved in morphogenesis.

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Functional conservation of Drosophila FTZ-F1 and its mammalian homologs suggests ligand-independent regulation of NR5A family transcriptional activity

Anderson

Zhang

et al. 2013

Dev Genes Evol

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Drosophila Ftz-F1 is an orphan nuclear receptor required for segmentation and metamorphosis. Its mammalian orthologs, SF-1 and LRH-1, function in sexual development and homeostasis, and have been implicated in stem cell pluripotency maintenance and tumorigenesis. These NR5A family members bind DNA as monomers and strongly activate transcription. However, controversy exists as to whether their activity is regulated by ligand-binding. Structural evidence suggested that SF-1 and human LRH-1 bind regulatory ligands, but mouse LRH-1 and Drosophila FTZ-F1 are active in the absence of ligand. We found that Dm-Ftz-F1 and mLRH-1, thought not to bind ligand, or mSF-1 and hLRH-1, predicted to bind ligand, each efficiently rescued the defects of Drosophila ftz-f1 mutants. Further, each correctly activated expression of a Dm-Ftz-F1 target gene in Drosophila embryos. The functional equivalence of ftz-f1 orthologs in these sensitive in vivo assays argues against specific activating ligands for NR5A family members.

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The Ftz‐F1 family: Orphan nuclear receptors regulated by novel protein–protein interactions

Cited by 17 publications

References 210 publications

The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition

The nuclear receptor gene nhr-25 plays multiple roles in the Caenorhabditis elegans heterochronic gene network to control the larva-to-adult transition

Stripy Ftz target genes are coordinately regulated by Ftz-F1

Functional conservation of Drosophila FTZ-F1 and its mammalian homologs suggests ligand-independent regulation of NR5A family transcriptional activity

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