title: Establishing and interpreting graded Sonic Hedgehog signaling during vertebrate neural tube patterning: the role of negative feedback.
abstract: The secreted protein Sonic Hedgehog (SHH) acts in graded fashion to pattern the dorsal-ventral axis of the vertebrate neural tube. This is a dynamic process in which increasing concentrations and durations of exposure to SHH generate neurons with successively more ventral identities. Interactions between the receiving cells and the graded signal underpin the mechanism of SHH action. In particular, negative feedback, involving proteins transcriptionally induced or repressed by SHH signaling, plays an essential role in shaping the graded readout. On one hand, negative feedback controls, in a noncell-autonomous manner, the distribution of SHH across the field of receiving cells. On the other, it acts cell-autonomously to convert different concentrations of SHH into distinct durations of intracellular signal transduction. Together, these mechanisms exemplify a strategy for morphogen interpretation, which we have termed temporal adaptation that relies on the continuous processing and refinement of the cellular response to the graded signal.
authors.affiliation: Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom, NW7 1AA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ribes
authors.forename: James
authors.initials: J
authors.lastname: Briscoe
mesh_terms: D000818:Animals; D019521:Body Patterning; D047108:Embryonic Development; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D054259:Neural Tube / Q000196:embryology*; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014714:Vertebrates
chemical_list: D053823:Hedgehog Proteins; D014157:Transcription Factors