The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors.
Xenopus blastula cells activate different mesodermal genes as a concentration-dependent response to activin, which behaves like a morphogen. To understand how cells recognize morphogen concentration, we have bound naturally labeled activin to cells and related this to choice of gene activation. We find that the increasing occupancy of a single receptor type can cause cells to switch gene expression. Cells sense ligand concentration by the absolute number of occupied receptors per cell (100 and 300 molecules of bound activin induce Xbra and Xgsc, respectively, i.e., 2% and 6% of the total receptors) and not by a ratio of occupied to unoccupied receptors. The long duration of occupancy explains a previously described ratchet effect. Our results suggest a new concept of morphogen gradient formation and interpretation that is particularly well suited to the needs of early development.
Dyson
S
S
Wellcome/CRC Institute, Cambridge, United Kingdom.
Gurdon
J B
JB
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D005326:Fetal Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D007265:Inhibins / Q000494:pharmacology; D008024:Ligands; D009842:Oligopeptides; D009865:Oocytes; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D015398:Signal Transduction / Q000502:physiology*; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation; D014981:Xenopus; D000098908:Brachyury Protein
D029404:Activin Receptors; D028341:Activins; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D007265:Inhibins; D008024:Ligands; D009842:Oligopeptides; D010455:Peptides; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C044147:activin B; C048617:myelopeptides