Figure 1: Optogenetic phase transition of TDP-43 in the motor neuron. (A) Structures of TDP-43 and opTDP-43. (B) Cytoplasmic TDP-43 in different forms may cause toxicity via distinct mechanisms. CRY2olig-driven opTDP-43 oligomerization promotes pathological changes in motor neurons, such as axon retraction, which is associated with myofiber denervation, prior to the accumulation of distinct cytoplasmic aggregates. Whether CRY2olig-driven opTDP-43 aggregates are toxic to motor neurons and whether CRY2olig-driven aggregates eventually deplete endogenous nuclear TDP-43 pools remain unknown. BL: Blue light; IDR: intrinsically disordered region; RRM: RNA-binging domain; TDP-43: cytoplasmic inclusions containing the transactivation response element DNA-binding protein-43.