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Gene Review

htl  -  heartless

Drosophila melanogaster

Synonyms: CG7223, CT22273, CT39172, DFGF-R1, DFGF-R2, ...
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High impact information on htl

  • We show that it also interacts genetically with the receptor tyrosine kinases Torso and Sevenless, and it was first discovered through its effect on FGF receptor signaling [1].
  • Embryos that lack ths+ and pyr+ exhibit defects related to those seen in htl mutants, including delayed mesodermal migration during gastrulation and a loss of cardiac tissues and hindgut musculature [2].
  • The two genes exhibit dynamic patterns of expression in epithelial tissues adjacent to Htl-expressing mesoderm derivatives, including the neurogenic ectoderm, stomadeum, and hindgut [2].
  • Thus, we propose that awd regulates tracheal cell motility by modulating the FGFR levels, through a dynamin-mediated pathway [3].
  • Moreover, DER and Htl are differentially involved in the specification of particular progenitors [4].

Biological context of htl

  • One of these genomic intervals produces upon its deletion a phenocopy of the htl cell migration phenotype [5].
  • These hybrid receptors can also rescue cell migration in the absence of Downstream of FGFR (Dof), a cytoplasmic protein essential for FGF signaling [6].
  • A potential binding site that matches this consensus is found in both Btl and Htl, located between the transmembrane and kinase domains of each receptor [7].
  • DFGF-R1 (breathless), a Drosophila FGF receptor homolog, is required for the migration of tracheal cells and the posterior midline glial cells during embryonic development [8].
  • The RhoGEF Pebble is required for cell shape changes during cell migration triggered by the Drosophila FGF receptor Heartless [9].

Anatomical context of htl


Associations of htl with chemical compounds

  • DFR1 and DFR2 proteins contain two and five immunoglobulin-like domains, respectively, in the extracellular region, and a split tyrosine kinase domain in the intracellular region [10].
  • Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development [13].

Regulatory relationships of htl


Other interactions of htl


Analytical, diagnostic and therapeutic context of htl


  1. Sprouty, an intracellular inhibitor of Ras signaling. Casci, T., Vinós, J., Freeman, M. Cell (1999) [Pubmed]
  2. pyramus and thisbe: FGF genes that pattern the mesoderm of Drosophila embryos. Stathopoulos, A., Tam, B., Ronshaugen, M., Frasch, M., Levine, M. Genes Dev. (2004) [Pubmed]
  3. Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development. Dammai, V., Adryan, B., Lavenburg, K.R., Hsu, T. Genes Dev. (2003) [Pubmed]
  4. Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm. Carmena, A., Gisselbrecht, S., Harrison, J., Jiménez, F., Michelson, A.M. Genes Dev. (1998) [Pubmed]
  5. FGF8-like1 and FGF8-like2 encode putative ligands of the FGF receptor Htl and are required for mesoderm migration in the Drosophila gastrula. Gryzik, T., Müller, H.A. Curr. Biol. (2004) [Pubmed]
  6. Specificity of FGF signaling in cell migration in Drosophila. Dossenbach, C., Röck, S., Affolter, M. Development (2001) [Pubmed]
  7. p120 Ras GTPase-activating protein associates with fibroblast growth factor receptors in Drosophila. Woodcock, S.A., Hughes, D.A. Biochem. J. (2004) [Pubmed]
  8. Elucidation of the role of breathless, a Drosophila FGF receptor homolog, in tracheal cell migration. Reichman-Fried, M., Dickson, B., Hafen, E., Shilo, B.Z. Genes Dev. (1994) [Pubmed]
  9. The RhoGEF Pebble is required for cell shape changes during cell migration triggered by the Drosophila FGF receptor Heartless. Schumacher, S., Gryzik, T., Tannebaum, S., Müller, H.A. Development (2004) [Pubmed]
  10. Two FGF-receptor homologues of Drosophila: one is expressed in mesodermal primordium in early embryos. Shishido, E., Higashijima, S., Emori, Y., Saigo, K. Development (1993) [Pubmed]
  11. Neuroglian and FasciclinII can promote neurite outgrowth via the FGF receptor Heartless. Forni, J.J., Romani, S., Doherty, P., Tear, G. Mol. Cell. Neurosci. (2004) [Pubmed]
  12. Heartless, a Drosophila FGF receptor homolog, is essential for cell migration and establishment of several mesodermal lineages. Beiman, M., Shilo, B.Z., Volk, T. Genes Dev. (1996) [Pubmed]
  13. Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development. Lin, X., Buff, E.M., Perrimon, N., Michelson, A.M. Development (1999) [Pubmed]
  14. Dynamic transcriptional regulatory complexes, including E2F4, p107, p130, and Sp1, control fibroblast growth factor receptor 1 gene expression during myogenesis. Parakati, R., DiMario, J.X. J. Biol. Chem. (2005) [Pubmed]
  15. heartless encodes a fibroblast growth factor receptor (DFR1/DFGF-R2) involved in the directional migration of early mesodermal cells in the Drosophila embryo. Gisselbrecht, S., Skeath, J.B., Doe, C.Q., Michelson, A.M. Genes Dev. (1996) [Pubmed]
  16. Sprouty is a general inhibitor of receptor tyrosine kinase signaling. Reich, A., Sapir, A., Shilo, B. Development (1999) [Pubmed]
  17. D-mef2: a Drosophila mesoderm-specific MADS box-containing gene with a biphasic expression profile during embryogenesis. Nguyen, H.T., Bodmer, R., Abmayr, S.M., McDermott, J.C., Spoerel, N.A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  18. Hindgut visceral mesoderm requires an ectodermal template for normal development in Drosophila. San Martin , B., Bate, M. Development (2001) [Pubmed]
  19. Repression of fibroblast growth factor receptor 1 gene expression by E2F4 in skeletal muscle cells. Parakati, R., Dimario, J.X. Dev. Dyn. (2005) [Pubmed]
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