BMP Signaling Gradient Scaling in the Zebrafish Pectoral Fin

Secreted growth factors can act as morphogens that form spatial concentration gradients in developing organs, thereby controlling growth and patterning. For some morphogens, adaptation of the gradients to tissue size allows morphological patterns to remain proportioned as the organs grow. In the zebrafish pectoral fin, we found that BMP signaling forms a two-dimensional gradient. The length of the gradient scales with tissue length and its amplitude increases with fin size according to a power-law. Gradient scaling and amplitude power-laws are signatures of growth control by time derivatives of morphogenetic signaling: cell division correlates with the fold change over time of the cellular signaling levels. We show that Smoc1 regulates BMP gradient scaling and growth in the fin. Smoc1 scales the gradient by means of a feedback loop: Smoc1 is a BMP agonist and BMP signaling represses Smoc1 expression. Our work uncovers a layer of morphogen regulation during vertebrate appendage development.

Taken together, our data suggest a scenario where the fin contains a proximal BMP source that generates a single gradient deployed along the proximo-distal axis, while signaling, as revealed by the BRE reporter, is only seen in the ROI. This is consistent with the presence of BMP signaling antagonists in the endoskeletal disc (Bauer et al., 1998, Fürthauer et al., 1999), which could decrease the signaling levels in the center of the endoskeletal disc. This could generate an effective scenario where two signaling gradients are deployed in the fin.

Further exploration into the specific properties of a fold change detection system during the embryonic growth of the pectoral fin will provide a general framework to understand growth and patterning of vertebrate appendages.