MRC National Institute for Medical Research, London
Science for Health
Embryonic development of the spinal cord is all about timing
04 June 2010
It has long been known that cells respond to chemical signals in embryonic tissues by activating distinct sets of genes and then becoming different cell types. These chemical signals are often referred to as morphogens and are produced in specific locations and at specific concentrations. They then spread into the surrounding tissue to form concentration gradients. Different target genes are activated at specific distances from the source of the morphogen, and therefore the spatial pattern of gene activity correlates with the concentration gradient.
James Briscoe (pictured) and his group in NIMR's Division of Developmental Neurobiology has explored how a morphogen gradient is perceived and interpreted by cells. In the spinal cord one well-known morphogen, Sonic Hedgehog (Shh), is responsible for the pattern in which different neurons and other cell types are produced. In a paper published this week in PLoS Biology they show that the duration of morphogen signalling is important for this. One consequence is that different cellular identities in the spinal cord appear to be assigned progressively with some cell types requiring signalling to be sustained for a longer time than others.
While this mechanism works for most cell types in the spinal cord, in a second paper, published in Genes and Development, James Briscoe's group shows that it does not apply to one specific and important group of spinal cord cells: the non-neuronal floor plate. Instead an earlier and biphasic signal from Shh is necessary. Moreover, in order for floor plate cells to differentiate, this signalling has then to be turned off. Together the two papers reveal new insight into how the spinal cord is formed in embryos, and highlight the importance of the timing and dynamics of morphogen signalling for the correct development of tissues.
These studies challenge some of the current views about how morphogens work and they suggest ways in which the usefulness of a single chemical signal can be extended during embryonic development. Understanding how cells respond to chemical signals during the embryonic development of the nervous system raises the possibility that we could direct stem cells to become specific types of nerve cells. This could be really useful in developing new therapies. Moreover, it’s possible that similar mechanisms are used elsewhere in the embryo to organize the development of other tissues.
James Briscoe
Neural tube patterning and the dynamics of Shh signaling
Original articles
The research findings are published in full in:
Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen Sonic Hedgehog
(2010) Eric Dessaud, Vanessa Ribes, Nikolaos Balaskas, Lin Lin Yang, Alessandra Pierani, Anna Kicheva, Ben Novitch, James Briscoe, Noriaki Sasai
PLoS Biology 8(6):e1000382. Full text
Distinct Sonic Hedgehog signalling dynamics specify floor plate and ventral neuronal progenitors in the vertebrate neural tube (2010)
Vanessa Ribes, Nikos Balaskas, Noriaki Sasai, Catarina Cruz, Eric Dessaud, Jordi Cayuso, Samuel Tozer, Lin Lin Yang, Ben Novitch, Elisa Marti, James Briscoe
Genes and Development 24:1186-1200. Publisher abstract
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