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

• During gastrulation Htl is required for adhesive interactions of the mesoderm with the ectoderm and for the generation of protrusive activity of the mesoderm cells during migration [5].
• FGF8-like1 and FGF8-like2 encode putative ligands of the FGF receptor Htl and are required for mesoderm migration in the Drosophila gastrula [5].
• At later stages, putative muscle precursor cells and cells in the central nervous system (CNS) express DFR1 [10].
• Neuroglian and FasciclinII can promote neurite outgrowth via the FGF receptor Heartless [11].
• The defective spreading could be circumvented in htl mutant embryos by providing an ectopic Dpp patterning signal, leading to the formation of heart and dorsal muscle cells [12].

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

• Developmentally controlled transcriptional regulation of myogenic cell proliferation and differentiation via expression of the fibroblast growth factor receptor 1 (FGFR1) gene is positively regulated by Sp1 and negatively regulated by E2F4-based transcriptional complexes [14].

Other interactions of htl

• BACKGROUND: Mesoderm migration in the Drosophila gastrula depends on the fibroblast growth factor (FGF) receptor Heartless (Htl) [5].
• Visceral mesoderm can nevertheless be induced by Dpp in the absence of htl function [15].
• Sprouty was originally identified as an inhibitor of Drosophila FGF receptor signaling during tracheal development [16].
• D-mef expression is not dependent on the function of tin, and embryos that are deficient for the mesodermal gene DFR1 also show normal initiation of D-mef2 expression at blastoderm [17].
• Wingless and the fibroblast growth factor receptor Heartless act over sequential but interdependent phases of hindgut visceral mesoderm development [18].

Analytical, diagnostic and therapeutic context of htl

• Gel shift assays detected E2F4 binding to a synthetic FGFR1 E2F4 binding site and chromatin immunoprecipitation assays detected E2F4 binding to the endogenous FGFR1 promoter in proliferating myoblasts and myotubes [19].

References