Model of the roles of PSD-95 and EB3 in regulating dendritogenesis. A, Under control conditions, EB3 comets have a lifetime of ∼10.5 s. This time is influenced by the cycling of EB3 on and off of the plus end of the microtubule and the cycles of microtubule catastrophe and rescue. Endogenous PSD-95 interacts with EB3. B, When PSD-95 or EB3-THR is overexpressed, EB3 comet lifetime decreases, leading to reduced dendritic complexity. EB3-THR comets remain on microtubules for a shorter amount of time than do wild-type comets, and increased PSD-95 expression may sequester EB3, reducing its lifetime at the plus end of microtubules. C, In control neurons, microtubules do not cross at branch points frequently. D, When PSD-95 is overexpressed, the frequency of microtubules that cross between dendritic branches increases. Scale bars in example images of neurons: 50 μm.