Signal integration during development: mechanisms of EGFR and Notch pathway function and cross-talk.
Metazoan development relies on a highly regulated network of interactions between conserved signal transduction pathways to coordinate all aspects of cell fate specification, differentiation, and growth. In this review, we discuss the intricate interplay between the epidermal growth factor receptor (EGFR; Drosophila EGFR/DER) and the Notch signaling pathways as a paradigm for signal integration during development. First, we describe the current state of understanding of the molecular architecture of the EGFR and Notch signaling pathways that has resulted from synergistic studies in vertebrate, invertebrate, and cultured cell model systems. Then, focusing specifically on the Drosophila eye, we discuss how cooperative, sequential, and antagonistic relationships between these pathways mediate the spatially and temporally regulated processes that generate this sensory organ. The common themes underlying the coordination of the EGFR and Notch pathways appear to be broadly conserved and should, therefore, be directly applicable to elucidating mechanisms of information integration and signaling specificity in vertebrate systems.
Doroquez
David B
DB
Department of Biology, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Rebay
Ilaria
I
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005136:Eye Proteins; D005786:Gene Expression Regulation; D008024:Ligands; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009024:Morphogenesis; D009419:Nerve Tissue Proteins; D020880:Neuregulins / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000033:anatomy & histology / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D029721:Drosophila Proteins; D005136:Eye Proteins; D008024:Ligands; D009419:Nerve Tissue Proteins; D020880:Neuregulins; D051880:Receptors, Notch; D016211:Transforming Growth Factor alpha; C075638:aos protein, Drosophila; C102104:vn protein, Drosophila; D066246:ErbB Receptors; D048490:raf Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D053829:Amyloid Precursor Protein Secretases; D018631:ras Proteins