“…The final structure of developing organs is determined by cell-to-extracellular matrix and cell-to-cell interactions alongside a series of changes in cellular abundance, shape, and position 133 . E3 ligases can drive these changes by regulating cell-cell fusion (e.g., CUL3-KCTD10 in muscle cell fusion 134 ), extracellular matrix degradation (e.g., RNF31-SHARPIN in mammary glands 135 ), cell migration (e.g., CUL3-BACURD1/2 and cortical neuron migration [136][137][138] ), epithelial-mesenchymal transition (e.g., SMURF2 in mammary glands 139 ), cytoskeletal/structural molecule stability (e.g., CUL3 regulating neuronal cytoskeletal dynamics and Rho signaling 140 and CUL3-Kelch proteins in skeletal muscle 141 ), and cell number (e.g., NEDD4 in the craniofacial complex 142 , CUL4 in the heart 143 , APC/C and MDM2 in the brain and lungs 144,145 )(Figure 2, 4, 5).…”