Losing your head

You know those people who seem to have lost their heads? Well, scientists have made a recent discovery into the molecular mechanism underlying that phenomena. Scientists from Vanderbilt University have discovered the two essential primary factors that specify vertebrate head and trunk formation. As published in Genes & Development, Dr. Encina Gonzalez and colleagues have discovered that the genes bozozok (boz) and chordino (din) cooperate in limiting the activity of the hormone, BMP, during embryological development, and thereby allow for head and trunk formation. This discovery uncovers a surprisingly simple mechanism of vertebrate head and trunk specification.

BMP hormones act as morphogens; they are molecules that specify cell fate in a concentration-dependent manner. Gradients of BMP activity in the embryo determine the body axis. Specific BMP inhibitors, or antagonists, help establish a gradient of decreasing BMP activity along the embryo. For example, the highest level of BMP activity signals cells to become skin and blood. Low levels of BMP activity signal cells to adopt neural fates. Abnormally high levels of BMP in the anterior portion of the embryo prevent the formation of the head and trunk. Thus, BMP antagonists are responsible for maintaining the fidelity of the embryonic body plan.

boz and din had already been molecularly characterized, but their integral role in head and trunk specification had gone unrecognized. Mutations in either one of these genes confers a mutant phenotype that is reminiscent of mildly excessive BMP activity. However, it was not until Dr. Gonzalez and colleagues made zebrafish with mutations in both of these genes, that the functional significance of boz and din became apparent. boz din double mutant embryos have no head or trunk, only a tail. This double mutant phenotype suggests that boz and din regulate separate but redundant pathways limiting BMP activity in the anterior portion of the embryo. Therefore, in boz din double mutants BMP activity is greatly expanded anteriorly. High BMP activity in the anterior portion of the developing embryo specifies that the cells which would normally form the head and trunk, become the tail.

This work by Dr. Gonzalez and colleagues represents the first time that the simultaneous disruption of two zygotic genes has resulted in vertebrate embryos without a head or trunk. In doing so, Dr. Gonzalez and colleagues have demonstrated that high levels of BMP activity in boz din double mutant embryos specifies posterior structures at the expense of anterior structures. That they were able to make embryos that have a tail instead of a head and trunk represents a dramatic advance in the understanding of vertebrate development.