Project Summary
The vertebral skeleton is a defining feature of vertebrates, yet little is known about how it grows and
evolves. To investigate the molecular genetic processes driving vertebral growth and proportion, we can look to
the tail with its vertebrae of simple geometry and extreme size differences between species. Although humans
do not have tails, many mammals use their tails to climb, balance, and communicate and have therefore evolved
tails of diverse lengths made up of different numbers of vertebrae with a range of sizes. The tail is therefore
highly evolvable and likely represents mechanisms of modular growth control used throughout the axial skeleton.
An example of tail diversity in closely related rodents is a comparison of the mouse (Mus musculus) and
the bipedal lesser Egyptian jerboa (Jaculus jaculus), which diverged from a common ancestor about 50 million
years ago. In addition to its more obviously exaggerated hindlimbs, the jerboa has evolved multiple changes to
the vertebral skeleton to support its upright posture, including elongation of individual vertebral elements. The
objective of this application is to define the temporal and cellular parameters of vertebral growth in mice
and jerboas, then use candidate and unbiased approaches to investigate the molecular mechanisms that
underlie vertebral growth rate differences. We hypothesize that local changes in gene expression and control
the ability of one bone to grow more or less than another. This hypothesis will be tested in the pursuit of three
specific aims: 1) Define the temporal and cellular parameters of vertebral growth that establishes and varies
proportion, 2) Reveal the role of natriuretic peptide signaling to drive vertebral growth and differential elongation
and, 3) Investigate gene expression differences associated with disproportionate vertebral growth. These aims
will be pursed using methods that are established in my laboratory or by collaboration, including: microCT and
X-ray imaging and histology, mouse knockout lines, and RNA sequencing. The proposed research takes
advantage of sound experimental approaches to understand naturally occurring vertebral variation and
phenotypes that are different from those observed in traditional model systems,The significance of these studies
lies in an opportunity to open a relatively unexplored area of skeletal biology that will contribute to our
understanding of body proportion development and evolution.
