Combinatorial signaling codes for the progressive determination of cell fates in the Drosophila embryonic mesoderm.
Mesodermal progenitors arise in the Drosophila embryo from discrete clusters of lethal of scute (l'sc)-expressing cells. Using both genetic loss-of-function and targeted ectopic expression approaches, we demonstrate here that individual progenitors are specified by the sequential deployment of unique combinations of intercellular signals. Initially, the intersection between the Wingless (Wg) and Decapentaplegic (Dpp) expression domains demarcate an ectodermal prepattern that is imprinted on the adjacent mesoderm in the form of a L'sc precluster. All mesodermal cells within this precluster are competent to respond to a subsequent instructive signal mediated by two receptor tyrosine kinases (RTKs), the Drosophila epidermal growth factor receptor (DER) and the Heartless (Htl) fibroblast growth factor receptor. By monitoring the expression of the diphosphorylated form of mitogen-associated protein kinase (MAPK), we found that these RTKs are activated in small clusters of cells within the original competence domain. Each cluster represents an equivalence group because all members initially resemble progenitors in their expression of both L'sc and mesodermal identity genes. Thus, localized RTK activity induces the formation of mesodermal equivalence groups. The RTKs remain active in the single progenitor that emerges from each cluster under the subsequent inhibitory influence of the neurogenic genes. Moreover, DER and Htl are differentially involved in the specification of particular progenitors. We conclude that distinct cellular identity codes are generated by the combinatorial activities of Wg, Dpp, EGF, and FGF signals in the progressive determination of embryonic mesodermal cells.
Carmena
A
A
Centro de Biologia Molecular 'Severo Ochoa', Universidad Autónoma, 28049 Madrid, Spain.
Gisselbrecht
S
S
Harrison
J
J
Jiménez
F
F
Michelson
A M
AM
D000818:Animals; D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D019521:Body Patterning; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002454:Cell Differentiation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics; D004627:Embryonic Induction; D004843:Epistasis, Genetic; D066246:ErbB Receptors / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D009132:Muscles / Q000166:cytology; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology; D018010:Receptors, Invertebrate Peptide / Q000502:physiology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics; D051155:Wnt1 Protein
D001426:Bacterial Proteins; D051792:Basic Helix-Loop-Helix Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D029721:Drosophila Proteins; D066246:ErbB Receptors; D018398:Homeodomain Proteins; D019476:Insect Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D017468:Receptors, Fibroblast Growth Factor; D018010:Receptors, Invertebrate Peptide; D014157:Transcription Factors; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C052837:eve protein, Drosophila; C089200:l(1)sc protein, Drosophila; C074622:wg protein, Drosophila; C066532:Egfr protein, Drosophila; C102667:htl protein, Drosophila