A Glutamine-Rich Factor Affects Stem Cell Genesis in Leech

Leech embryogenesis is a model for investigating cellular and molecular processes of development. Due to the unusually large size of embryonic stem cells (teloblasts; 50 - 300 μm) in the glossiphoniid leech, Theromyzon tessulatum, and the presence of identifiable stem cell precursors (proteloblasts), we previously isolated a group of genes up-regulated upon stem cell birth. In the current study, we show that one of these genes, designated Tpr (Theromyzon proliferation), is required for normal stem cell genesis; specifically, transient Tpr knockdown experiments conducted with antisense oligonucleotides and monitored by semi-quantitative RT-PCR, caused abnormal proteloblast proliferation leading to embryonic death, but did not overtly affect neuroectodermal or mesodermal stem cell development once these cells were born. Tpr encodes a large, glutamine-rich (~34%) domain that shares compositional similarity with strong transcriptional enhancers, many of which have been linked with trinucleotide repeat disorders (e.g., Huntingtons).