Stochastic WNT signaling between nonequivalent cells regulates adhesion but not fate in the two-cell leech embryo

Background: In the leech Helobdella robusta, an annelid worm, the early pat tern of cell divisions is stereotyped. The unequal first cleavage yields ce lls AB and CD, which differ in size. cytoplasmic inheritance, normal fate, and developmental potential. Results: Here we report a dynamic and transcription-independent pattern of WNT signaling in the two-cell stage of H. robusta. Surprisingly, HRO-WNT-A is first expressed in a stochastic manner, such that either AB or CD secret es the protein in each embryo. This stochastic phase is followed by a deter ministic phase during which first AB, then CD expresses HRO-WNT-A, When con tact between the cells is reduced or eliminated, both AB and CD express HRO -WNT-A simultaneously. Finally, bathing embryos in anti-HRO-WNT-A antibody during first cleavage reduces the adhesion between cells AB and CD. Conclusions: Our findings show that the stochastic phase of HRO-WNT-A signa ling in the two-cell stage of Helobdella is negatively regulated by cell-ce ll contact and that this early signaling affects cell adhesion without affe cting cell fate. We speculate that the primordial function of wnt class gen es may have been to regulate cell-cell adhesion and that the nuclear signal ing components of the wnt pathway arose later in association with the evolu tion of diverse cell types.