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Spinal cord development sets up all neurons
In order for embryos to grow and develop, they need the right cell types to be in the right places before organs can form. This is particularly important in the spinal cord where different types of nerve cells must be accurately positioned before circuits that control muscle movement can assemble. Before this research, mechanisms underlying nerve cell organization were poorly understood. The study is published in the journal Science.
Researchers at the Francis Crick Institute, the Institute of Science and Technology (Austria) and Ecole Polytechnique Fédérale de Lausanne (Switzerland) report that cells destined to become nerve cells in mouse embryos become organized in response to two different signals emminating from opposite sides of the mouse spinal cord.
The research was funded by the European Research Council and the Wellcome Trust, a biomedical research charity based in London, United Kingdom.
It took a team of biologists, physicists and engineers to identify that a variation in the volume of signals sent from the back and belly of the mouse, can affect the activity of genes developing into nerve cells. Based on this gene activity in early development, precursor neural cells can now become the appropriate nerve cell type in various positions relative to the spinal cord.
"We've made an important step in understanding how the diverse cell types in the spinal cord of a developing embryo are organized in a precise spatial pattern," explains Anna Kicheva PhD, assistant professor of Tissue Growth and Developmental Pattern Formation, at the Institute of Science and Technology 1ST Austria, Vienna, Austria, as well as group leader at 1ST Austria. "The quantitative measurements and new experimental techniques we used, as well as the combined effort of biologists, physicists and engineers were key. This allowed us to gain new insight into the exquisite accuracy of embryonic development and revealed that cells have remarkable ability of to orchestrate precise tissues in development."
"We have shed light on the long-standing question of how developing tissues produce the right cells in the right place in the right numbers," adds James Briscoe, Group Leader at the Francis Crick Institute. "It's likely that similar strategies are used in other developing tissues and our findings might be relevant to these cases. In the long run this will help inform the use of stem cells in approaches such as tissue engineering and regenerative medicine. However, there is still much more to learn and we need to continue developing these interdisciplinary collaborations to further our biological understanding."
Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured morphogen signaling and target gene expression in mouse embryos and chick ex vivo assays. From these data, we derived and validated a characteristic decoding map that relates morphogen input to the positional identity of neural progenitors. Analysis of the observed responses indicates that the underlying interpretation strategy minimizes patterning errors in response to the joint input of noisy opposing gradients. We reverse-engineered a transcriptional network that provides a mechanistic basis for the observed cell fate decisions and accounts for the precision and dynamics of pattern formation. Together, our data link opposing gradient dynamics in a growing tissue to precise pattern formation.
Other authors: Marcin Zagorski, Yoji Tabata, Nathalie Brandenberg, Matthias P. Lutolf, Gašper Tka?ik, Tobias Bollenbach
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A normal developing spinal cord (left) reflects patterns of gene activity delineated in
red, blue, and green to represent differently developing cell types. (Right) A spinal cord in
which one of the signals is disrupted reflects how accurate allignment of genes is lost.
Image Credit: Anna Kicheva PhD