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Gene Review

fkh  -  fork head

Drosophila melanogaster

Synonyms: CG10002, Dmel\CG10002, Dmfkh, FKH, Fkh, ...
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Disease relevance of fkh


High impact information on fkh

  • Moreover, interfering with InR signaling exclusively in the heart, by overexpressing the phosphatase dPTEN or the forkhead transcription factor dFOXO, prevents the decline in cardiac performance with age [2].
  • The region-specific homeotic gene fork head (fkh) promotes terminal as opposed to segmental development in the Drosophila embryo [3].
  • The fkh gene product, however, does not contain a known protein motif, such as the homeodomain or the zinc fingers, nor is it similar in sequence to any other known protein [3].
  • P element-mediated germ-line transformation and sequence comparison of wild-type and mutant alleles identify the fkh gene within the cloned region. fkh is expressed in the early embryo in the two terminal domains that are homeotically transformed in fkh mutant embryos [3].
  • The Drosophila forkhead transcription factor (dFOXO) activates d4E-BP transcription [4].

Biological context of fkh


Anatomical context of fkh

  • Our findings suggest at least two roles for fkh in formation of the embryonic salivary glands: an early role in promoting survival of the secretory cells, and a later role in secretory cell invagination, specifically in the constriction of the apical surface membrane [6].
  • In embryos mutant for fork head (fkh), which encodes a transcription factor homologous to mammalian hepatocyte nuclear factor 3beta (HNF-3beta), the secretory primordia are not internalized and secretory tubes do not form [6].
  • The rescued fkh secretory cells undergo basal nuclear migration in the same spatial and temporal pattern as in wild-type secretory cells, but do not constrict their apical surface membranes [6].
  • Metabolic Diapause in Pancreatic beta-Cells Expressing a Gain-of-function Mutant of the Forkhead Protein Foxo1 [1].
  • Our knowledge of endoderm development is limited; however, recent studies suggest that cooperation between the HNF3/Fork head and GATA transcription factors is crucial for endoderm specification [8].

Associations of fkh with chemical compounds

  • Two of the Fork head/SEBP2 binding sites are located within an ecdysone response unit which controls the tissue- and stage-specific responses of Sgs-4 to the steroid hormone 20-hydroxyecdysone [5].
  • Functional analyses show decreased glucose utilization and insulin secretion in beta-cells overexpressing Foxo1 [1].
  • By applying this method to many motifs and to a cluster set of yeast genes, we detected a similarity between Swi Five Factor and forkhead proteins and suggest that the currently unidentified Swi Five Factor is one of the yeast forkhead proteins [9].

Physical interactions of fkh

  • Mobility shift assay in the presence of an anti-Fork head antibody demonstrated that the Fork head factor interacts with the TGTTTGC box shown to be involved in tissue-specific Sgs3 expression [10].

Regulatory relationships of fkh

  • Our results allow efficient recognition of insect Fork head binding sites and we show that the putative Fork head cognate elements preferentially accumulate in the near upstream region of genes abundantly expressed in the labial gland [11].

Other interactions of fkh

  • We propose that trh, hkb, and fkh may serve as "morphogenetic cassettes" responsible for forming tubular structures in a variety of tissues [12].
  • We present a model proposing that trachealess is the crucial duct-specific gene that Fork head represses to distinguish pregland from preduct cells [13].
  • We characterize a 37-bp element (fkh[250]) derived from the fork head (fkh) gene, a natural target of the Hox gene Sex combs reduced (Scr) [14].
  • We have shown that sens expression is initiated in the salivary placodes by fork head (fkh), a winged helix transcription factor [15].
  • Downregulation of the tissue-specific transcription factor Fork head by Broad-Complex mediates a stage-specific hormone response [16].

Analytical, diagnostic and therapeutic context of fkh


  1. Metabolic Diapause in Pancreatic beta-Cells Expressing a Gain-of-function Mutant of the Forkhead Protein Foxo1. Buteau, J., Shlien, A., Foisy, S., Accili, D. J. Biol. Chem. (2007) [Pubmed]
  2. Insulin regulation of heart function in aging fruit flies. Wessells, R.J., Fitzgerald, E., Cypser, J.R., Tatar, M., Bodmer, R. Nat. Genet. (2004) [Pubmed]
  3. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Weigel, D., Jürgens, G., Küttner, F., Seifert, E., Jäckle, H. Cell (1989) [Pubmed]
  4. Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP. Tettweiler, G., Miron, M., Jenkins, M., Sonenberg, N., Lasko, P.F. Genes Dev. (2005) [Pubmed]
  5. The fork head product directly specifies the tissue-specific hormone responsiveness of the Drosophila Sgs-4 gene. Lehmann, M., Korge, G. EMBO J. (1996) [Pubmed]
  6. Fork head prevents apoptosis and promotes cell shape change during formation of the Drosophila salivary glands. Myat, M.M., Andrew, D.J. Development (2000) [Pubmed]
  7. Salivary gland determination in Drosophila: a salivary-specific, fork head enhancer integrates spatial pattern and allows fork head autoregulation. Zhou, B., Bagri, A., Beckendorf, S.K. Dev. Biol. (2001) [Pubmed]
  8. Functional specification in the Drosophila endoderm. Nakagoshi, H. Dev. Growth Differ. (2005) [Pubmed]
  9. Assessing clusters and motifs from gene expression data. Jakt, L.M., Cao, L., Cheah, K.S., Smith, D.K. Genome Res. (2001) [Pubmed]
  10. The Drosophila fork head factor directly controls larval salivary gland-specific expression of the glue protein gene Sgs3. Mach, V., Ohno, K., Kokubo, H., Suzuki, Y. Nucleic Acids Res. (1996) [Pubmed]
  11. The DNA binding of insect Fork head factors is strongly influenced by the negative cooperation of neighbouring bases. Takiya, S., Gazi, M., Mach, V. Insect Biochem. Mol. Biol. (2003) [Pubmed]
  12. Early genes required for salivary gland fate determination and morphogenesis in Drosophila melanogaster. Myat, M.M., Isaac, D.D., Andrew, D.J. Adv. Dent. Res. (2000) [Pubmed]
  13. Salivary duct determination in Drosophila: roles of the EGF receptor signalling pathway and the transcription factors fork head and trachealess. Kuo, Y.M., Jones, N., Zhou, B., Panzer, S., Larson, V., Beckendorf, S.K. Development (1996) [Pubmed]
  14. The control of trunk Hox specificity and activity by Extradenticle. Ryoo, H.D., Mann, R.S. Genes Dev. (1999) [Pubmed]
  15. senseless is necessary for the survival of embryonic salivary glands in Drosophila. Chandrasekaran, V., Beckendorf, S.K. Development (2003) [Pubmed]
  16. Downregulation of the tissue-specific transcription factor Fork head by Broad-Complex mediates a stage-specific hormone response. Renault, N., King-Jones, K., Lehmann, M. Development (2001) [Pubmed]
  17. Survey of forkhead domain encoding genes in the Drosophila genome: Classification and embryonic expression patterns. Lee, H.H., Frasch, M. Dev. Dyn. (2004) [Pubmed]
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