We continued our analysis by asking if Erk waves regulate other aspects of osteoblast regeneration. We discovered that Erk waves modulate the transcription of the bone maturation transcription factor osterix, which is activated in trailing transcriptional waves.

We found that the abundance of inhibitor transcripts depends on Erk activity through Rectified Linear Unit (ReLU) responses: transcript levels increase linearly with Erk activity once a threshold is crossed.

To understand how refractory periods arise, we analyzed transcriptional patterns. Together with the Voigt lab at UZH, we developed an smFISH technique for whole-mount scales. This revealed that Erk waves induce beautiful trailing waves of the inhibitor transcripts dusp5, spry2, and spry4.

We further noticed that, when two waves meet, they merge, which suggests that waves are followed by regions that are refractory to Erk activation. This refractory region is predicted to result from high concentrations of Erk inhibitors, induced by Erk itself.

Erk waves were proposed to result from an excitable system including interactions with Erk activators and inhibitors. Compatibly with excitable Erk waves theory, we observed that Erk waves can form striking spiral patterns in scales.

The lab’s first pre-print! We investigated how growth-inducing Erk activity waves are regulated in regenerating zebrafish scales. We discovered that Erk waves are followed by waves of expression of their own inhibitors, as predicted by excitable waves theory. tinyurl.com/26r2cmpj