Dessaud, Éric; Ribes, Vanessa; Balaskas, Nikolaos; Yang, Linlin; Pierani, Alessandra; Kicheva, AnnaISTA ; Novitch, Bennett; Briscoe, James; Sasai, Noriaki
Morphogens are secreted signalling molecules that act in a graded manner to control the pattern of cellular differentiation in developing tissues. An example is Sonic hedgehog (Shh), which acts in several developing vertebrate tissues, including the central nervous system, to provide positional information during embryonic patterning. Here we address how Shh signalling assigns the positional identities of distinct neuronal subtype progenitors throughout the ventral neural tube. Assays of intracellular signal transduction and gene expression indicate that the duration as well as level of signalling is critical for morphogen interpretation. Progenitors of the ventral neuronal subtypes are established sequentially, with progressively more ventral identities requiring correspondingly higher levels and longer periods of Shh signalling. Moreover, cells remain sensitive to changes in Shh signalling for an extended time, reverting to antecedent identities if signalling levels fall below a threshold. Thus, the duration of signalling is important not only for the assignment but also for the refinement and maintenance of positional identity. Together the data suggest a dynamic model for ventral neural tube patterning in which positional information corresponds to the time integral of Shh signalling. This suggests an alternative to conventional models of morphogen action that rely solely on the level of signalling.
NS was supported by a Marie Curie Fellowship (PIIF-GA-2008-219939) and the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Support for VR was provided by an EMBO LTF, for AK by a FEBS LTF. ED was supported by the Wellcome Trust (#080630). Work in the lab of JB is supported by the Medical Research Council (UK). AP is a CNRS (Centre National de la Recherche Scientifique) Investigator. This work was supported by grants from the Ministère de la Recherche (ACI Grant #0220575) and the Association pour la Recherche sur le Cancer (Grant #4679) to AP. BGN was supported by grants from the Whitehall Foundation (2004-05-90-APL), the March of Dimes Foundation (5-FY2006-281), the Muscular Dystrophy Association (92901), and the NINDS (NS053976)
Dessaud É, Ribes V, Balaskas N, et al. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog. PLoS Biology. 2010;8(6). doi:10.1371/journal.pbio.1000382
Dessaud, É., Ribes, V., Balaskas, N., Yang, L., Pierani, A., Kicheva, A., … Sasai, N. (2010). Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.1000382
Dessaud, Éric, Vanessa Ribes, Nikolaos Balaskas, Linlin Yang, Alessandra Pierani, Anna Kicheva, Bennett Novitch, James Briscoe, and Noriaki Sasai. “Dynamic Assignment and Maintenance of Positional Identity in the Ventral Neural Tube by the Morphogen Sonic Hedgehog.” PLoS Biology. Public Library of Science, 2010. https://doi.org/10.1371/journal.pbio.1000382.
É. Dessaud et al., “Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog,” PLoS Biology, vol. 8, no. 6. Public Library of Science, 2010.
Dessaud É, Ribes V, Balaskas N, Yang L, Pierani A, Kicheva A, Novitch B, Briscoe J, Sasai N. 2010. Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen sonic hedgehog. PLoS Biology. 8(6).
Dessaud, Éric, et al. “Dynamic Assignment and Maintenance of Positional Identity in the Ventral Neural Tube by the Morphogen Sonic Hedgehog.” PLoS Biology, vol. 8, no. 6, Public Library of Science, 2010, doi:10.1371/journal.pbio.1000382.