The BMP ligand Pinhead together with Admp supports the robustness of embryonic patterning

Abstract

Vertebrate embryonic dorsoventral axis is robustly stable in the face of variations in bone morphogenetic protein (BMP) signaling. However, the molecular mechanism behind this robustness remains uncharacterized. In this study, we show that zebrafish Pinhead, together with Admp, plays an important compensatory role in ensuring the robustness of axial patterning through fine-tuning of BMP signaling. <i>pinhead</i> encodes a BMP-like ligand expressed in the ventrolateral margin of the early gastrula. Transcription of <i>pinhead</i> and <i>admp</i> is under opposing regulation, where <i>pinhead</i> depletion results in a compensatory increase in <i>admp</i> transcription and vice versa, leading to normal axis formation in <i>pinhead</i> or <i>admp</i> mutants. Expression of <i>pinhead</i> and <i>admp</i> is directly repressed by the BMP/Smad pathway. When BMP signals were inhibited or excessively activated, <i>pinhead</i>/<i>admp</i> expression changed accordingly, allowing for self-regulation. Thus, this study reveals a negative feedback loop between BMP signaling and <i>pinhead/admp</i> that effectively stabilizes embryonic patterning by buffering against fluctuations in BMP signaling.