Integration of Nodal and BMP Signaling by Mutual Signaling Effector Antagonism

oleh: Gary Huiming Soh, Autumn Penecilla Pomreinke, Patrick Müller

Format: Article
Diterbitkan: Elsevier 2020-04-01

Deskripsi

Summary: Opposing sources of bone morphogenetic protein (BMP) and Nodal signaling molecules are sufficient to induce the formation of a full axis in zebrafish embryos. To address how these signals orchestrate patterning, we transplant sources of fluorescently tagged Nodal and BMP into zebrafish embryos, robustly inducing the formation of secondary axes. Nodal and BMP signal non-cell-autonomously and form similar protein gradients in this context, but the signaling range of Nodal (pSmad2) is shorter than the BMP range (pSmad5). This yields a localized region of pSmad2 activity around the Nodal source, overlapping with a broad domain of pSmad5 activity across the embryo. Cell fates induced in various regions stereotypically correlate with pSmad2-to-pSmad5 ratios and can even be induced BMP- and Nodal-independently with different ratios of constitutively active Smad2 and Smad5. Strikingly, we find that Smad2 and Smad5 antagonize each other for specific cell fates, providing a mechanism for how cells integrate and discriminate between overlapping signals during development. : Juxtaposed Nodal and BMP sources can induce the formation of a secondary axis in zebrafish embryos. Soh et al. analyze the input-output relationships in this patterning system and find that differential signaling kinetics lead to different activity ranges of Nodal and BMP, which are crucial for secondary axis formation. Keywords: Nodal, BMP, zebrafish, embryo, development, Smad2, Smad5, gradients, axis induction