2016

Defining the basic mechanisms behind regeneration requires comparison to both development and homeostasis. How is organ size achieved in animals during normal development, and how is it reconstituted in animals capable of regenerating organs and body parts lost to injury? Are the mechanisms regulating size and allometry evolutionarily conserved? In recent years, discoveries in the fields of signaling, physiology, developmental biology and regeneration using a growing and diverse collection of model organisms have begun to shed mechanistic insight into these problems. Growth, central to embryonic development, tissue homeostasis and regeneration, was the unifying concept at the recent Molecular and Cellular Basis for Growth and Regeneration Keystone meeting.

Loss of heterozygosity through inbreeding or mitotic errors leads to reductions in progeny survival and fertility. Loss of heterozygosity is particularly exacerbated in geographically isolated populations, which are prone to inbreeding depression and faster rates of extinction. The regenerative capacities of the hermaphroditic biotype of the planarian Schmidtea mediterranea allowed us to perform a systematic genetic test of Mendelian segregation and study the loss of heterozygosity in the Spiralian superclade in general and planarians in particular. We discovered that ~300 Mb (~37.5%) of the genome retains heterozygosity even after ten generations of inbreeding, and show that these chromosomal regions have low diversity and recombination rates in wild populations. Our genetic and genomic analyses establish S. mediterranea as a genetically tractable system. The research also opens the door to study the evolutionary basis of non-Mendelian mechanisms, the adaptive advantages of chromosome structural heterozygotes and their potential relationship to the robust regenerative capacities of planarians.