heartless encodes a fibroblast growth factor receptor (DFR1/DFGF-R2) involved in the directional migration of early mesodermal cells in the Drosophila embryo.
After invagination of the mesodermal primordium in the gastrulating Drosophila embryo, the internalized cells migrate in a dorsolateral direction along the overlying ectoderm. This movement generates a stereotyped arrangement of mesodermal cells that is essential for their correct patterning by later position-specific inductive signals. We now report that proper mesodermal cell migration is dependent on the function of a fibroblast growth factor (FGF) receptor encoded by heartless (htl). In htl mutant embryos, the mesoderm forms normally but fails to undergo its usual dorsolateral migration. As a result, cardiac, visceral, and dorsal somatic muscle fates are not induced by Decapentaplegic (Dpp), a transforming growth factor beta family member that is derived from the dorsal ectoderm. Visceral mesoderm can nevertheless be induced by Dpp in the absence of htl function. Ras1 is an important downstream effector of Htl signaling because an activated form of Ras1 partially rescues the htl mutant phenotype. The evolutionary conservation of htl function is suggested by the strikingly similar mesodermal migration and patterning phenotypes associated with FGF receptor mutations in species as diverse as nematode and mouse. These studies establish that Htl signaling provides a vital connection between initial formation of the embryonic mesoderm in Drosophila and subsequent cell-fate specification within this germ layer.
Gisselbrecht
S
S
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Skeath
J B
JB
Doe
C Q
CQ
Michelson
A M
AM
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002465:Cell Movement / Q000235:genetics*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins; D017125:Genes, Protozoan / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics / Q000502:physiology; D006321:Heart / Q000196:embryology*; D008648:Mesoderm / Q000737:chemistry / Q000166:cytology*; D008969:Molecular Sequence Data; D009132:Muscles / Q000196:embryology; D009154:Mutation; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000502:physiology
D029721:Drosophila Proteins; D017468:Receptors, Fibroblast Growth Factor; D011505:Protein-Tyrosine Kinases; C102667:htl protein, Drosophila