Notch signaling patterns Drosophila mesodermal segments by regulating the bHLH transcription factor twist.
One of the first steps in embryonic mesodermal differentiation is allocation of cells to particular tissue fates. In Drosophila, this process of mesodermal subdivision requires regulation of the bHLH transcription factor Twist. During subdivision, Twist expression is modulated into stripes of low and high levels within each mesodermal segment. High Twist levels direct cells to the body wall muscle fate, whereas low levels are permissive for gut muscle and fat body fate. We show that Su(H)-mediated Notch signaling represses Twist expression during subdivision and thus plays a critical role in patterning mesodermal segments. Our work demonstrates that Notch acts as a transcriptional switch on mesodermal target genes, and it suggests that Notch/Su(H) directly regulates twist, as well as indirectly regulating twist by activating proteins that repress Twist. We propose that Notch signaling targets two distinct 'Repressors of twist' - the proteins encoded by the Enhancer of split complex [E(spl)C] and the HLH gene extra machrochaetae (emc). Hence, the patterning of Drosophila mesodermal segments relies on Notch signaling changing the activities of a network of bHLH transcriptional regulators, which, in turn, control mesodermal cell fate. Since this same cassette of Notch, Su(H) and bHLH regulators is active during vertebrate mesodermal segmentation and/or subdivision, our work suggests a conserved mechanism for Notch in early mesodermal patterning.
Tapanes-Castillo
Alexis
A
Program in Developmental Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, Weill Graduate School of Medical Sciences at Cornell University, 1275 York Avenue, New York, NY 10021, USA.
Baylies
Mary K
MK
D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000502:physiology; D002455:Cell Division; D017931:DNA Primers; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D009024:Morphogenesis / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051880:Receptors, Notch; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D051879:Twist-Related Protein 1
D017931:DNA Primers; D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1