Fig. 8.

Summary of WDR47 working model. At the cellular level, WDR47 acts as a stabilizer of microtubules. SCG10, a microtubule destabilizer at the growth cone, is regulated by JNK1 through phosphorylation. In the cytoplasm, WDR47 negatively regulates p62 and LC3-mediated autophagy. Reduced expression of Wdr47 leads to destabilization of the microtubules, increased Tau and autophagic flux, and decreased cell motility. At the tissue level, the loss of Wdr47 yields fiber tract defects, including corpus callosum agenesis, microcephaly, and thinner cortices, that are linked to a reduced number of progenitors, increased number of neurons in the intermediate zone, and elevated number of dying neurons in the cortical upper layers. At the organism level, these defects may explain impairment in motor coordination, reduced grip strength, and increased pain sensitivity. AP, apical progenitor; IP, intermediate progenitor; MN, migrating neuron; MT, microtubule.