A novel invertebrate trophic factor related to invertebrate neurotrophins is involved in planarian body regional survival and asexual reproduction.

Trophic factors are a heterogeneous group of molecules that promote cell growth and survival. In freshwater planarians, the small secreted protein TCEN49 is linked to the regional maintenance of the planarian central body region. To investigate its function in vivo, we performed loss-of-function and gain-of-function experiments by RNA interference and by the implantation of microbeads soaked in TCEN49, respectively. We show that TCEN49 behaves as a trophic factor involved in central body region neuron survival. In planarian tail regenerates, tcen49 expression inhibition by double-stranded RNA interference causes extensive apoptosis in various cell types, including nerve cells. This phenotype is rescued by the implantation of microbeads soaked in TCEN49 after RNA interference. On the other hand, in organisms committed to asexual reproduction, both tcen49 mRNA and its protein are detected not only in the central body region but also in the posterior region, expanding from cells close to the ventral nerve chords. In some cases, the implantation of microbeads soaked in TCEN49 in the posterior body region drives organisms to reproduce asexually, and the inhibition of tcen49 expression obstructs this process, suggesting a link between the central nervous system, TCEN49, regional induction, and asexual reproduction. Finally, the distribution of TCEN49 cysteine and tyrosine residues also points to a common evolutionary origin for TCEN49 and molluscan neurotrophins.