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

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. pinhead encodes a BMP-like ligand expressed in the ventrolateral margin of the early gastrula. Transcription of pinhead and admp is under opposing regulation, where pinhead depletion results in a compensatory increase in admp transcription and vice versa, leading to normal axis formation in pinhead or admp mutants. Expression of pinhead and admp is directly repressed by the BMP/Smad pathway. When BMP signals were inhibited or excessively activated, pinhead/admp expression changed accordingly, allowing for self-regulation. Thus, this study reveals a negative feedback loop between BMP signaling and pinhead/admp that effectively stabilizes embryonic patterning by buffering against fluctuations in BMP signaling.