The ErbB family of proteins comprises four receptor tyrosine kinases, including ErbB2 and ErbB3. ErbB2–ErbB3 heterodimers act as an oncogenic unit to drive tumour progression; however, very little is known about the function of this receptor combination during physiological processes. Having previously shown that cells of the human extravillous trophoblast (EVT) lineage express ErbB2 and ErbB3, suggesting a potential role for these receptors in placental development, Jürgen Pollheimer and colleagues now investigate the ErbB2–ErbB3 axis in EVT formation (p. ). The authors show that human decidual stromal cells express and secrete neuregulin 1 (NRG1), which induces the formation of ErbB2–ErbB3 dimers in human primary trophoblasts. Next, functional studies demonstrate that NRG1 promotes EVT formation in placental explant cultures. Moreover, NRG1 strongly suppresses basal rates of apoptosis, as well as camptothecin-induced apoptosis, in trophoblasts. This effect is abolished following inhibition of ErbB3. Finally, the authors show that cell columns treated with camptothecin were considerably reduced in size, whereas NRG1-treated explants were unaffected. Taken together, these data identify, for the first time, a physiological role for the NRG1–ErbB2–ErbB3 axis in the development of the human placenta.
