Successful embryonic development requires the reproducible formation of organs with the right shape. In the current framework for how complex organs arise from simple tissues (morphogenesis), developmental genes pattern cellular mechanics to drive tissue remodeling. This hierarchical framework, however, fails to account for interactions with extracellular players (like the extracellular matrix or ECM) and feedbacks across scales. To address these outstanding challenges in embryonic development, our lab leverages interdisciplinary approaches in an exemplary organ common to all vertebrates— the inner ear semicircular canals in zebrafish. The precise form of the canals is required for their function to maintain balance.  My postdoc work showed that the local synthesis of hyaluronic acid (HA) in the ECM generates mechanical forces through osmotic swelling to drive canal morphogenesis. HA synthesis is downregulated upon completion of morphogenesis. The spatial patterning and temporal regulation of HA synthesis have remained unknown. In our lab, we have identified a secreted ECM-associated growth factor (ccn1l1) as one of the key developmental regulators for proper canal formation by inducing the local patterning of HA. Quantitative expression mapping shows that ccn1l1 is dynamically expressed– low expression precedes the onset of morphogenesis, high expression during, and no expression upon completion of the process. Remarkably, inhibition of hyaluronate pressure inhibited the high ccn1l1 expression. Conversely, inhibition of cAMP signaling through an adhesive GPCR caused ccn1l1 expression for longer, leading to increased HA synthesis. With these results, we identify multi-scale feedback interactions: ccn1l1 is required for HA synthesis, and hyaluronate pressure, in turn, is required to amplify ccn1l1 expression (positive feedback); furthermore, the morphological change from this positive feedback likely activates cAMP signaling to shut down HA synthesis (negative feedback). We are investigating the mechanisms underlying these feedbacks and their roles in building proper tissue morphologies. Such feedback interactions across scales (from genes to cellular signaling to tissue remodeling and back) might apply to other developing tissues for robust morphogenesis.