Deciphering the regulatory network governing vertebral segmentation
One of the challenges in developmental biology is to explain how morphological changes and cell differentiation are executed via a cascade of regulatory steps. Here we studied the regulatory cascade controlling somite segment boundary formation. Somites, the rudiments of the body segments of a vertebrate, are produced sequentially from the presomitic mesoderm (PSM) at the tail end of the embryo as the PSM tissue grows. In the zebrafish, one new somite splits off from the anterior end of the PSM every 30 minutes, and this periodicity correlates with, and is controlled by, a 30-minute oscillation cycle in the expression of a set of genes in the posterior part of the PSM. This gene-expression oscillator is called the segmentation clock. We would like to understand how the clock leaves its trace in the periodic spatial pattern of the somites.
We previously described experiments in which we used a heat shock to overexpress the clock gene her7 throughout the PSM (Giudicelli et al 2007). Although gene expression oscillations are arrested uniformly in the PSM, to our surprise, this had no effect on the multiple somites that formed immediately after the heat shock, but disrupted somite segmentation posterior to these. From this, we could infer that the clock exerts its influence on the somite segmentation pattern while cells are in the posterior half of the PSM, but that once the future somite cells have moved into the anterior half of the PSM, the clock becomes functionally irrelevant, even though it continues to be expressed. How temporal information from gene expression oscillations is passed on to the rhythmic segmental patterning of cells ahead of time has remained elusive. We hypothesize that a set of readout genes function in anterior PSM cells and relay the temporal information from the segmentation clock to the segment boundaries. Discovering the regulatory network that integrates the segmentation clock with somite segmentation is significant for understanding, and potentially preventing, various types of vertebral malformations.
