  An intriguing unanswered question about the evolution of bilateral animals
with internal skeletons is how an internal skeleton evolved in the first place.
Computational modeling of the development of bilateral symmetric organisms
suggests an answer to this question. Our hypothesis is that an internal
skeleton may have evolved from a bilaterally symmetric ancestor with an
external skeleton. By growing the organism inside-out an external skeleton
becomes an internal skeleton. Our hypothesis is supported by a computational
theory of bilateral symmetry that allows us to model and simulate this process.
Inside-out development is achieved by an orientation switch. Given the
development of two bilateral founder cells that generate a bilateral organism,
a mutation that reverses the internal mirror orientation of those bilateral
founder cells leads to inside-out development. The new orientation is
epigenetically inherited by all progeny. A key insight is that each cell
contained in the newly evolved organism with the internal skeleton develops
according to the very same downstream developmental control network that
directs the development of its exoskeletal ancestor. The networks and their
genomes are are identical, but the interpretation is different because of the
cell's inverted orientation. The result is inside-out bilateral symmetric
development generating an inside-out organism with an internal skeleton.
