DECIPHERING THE ROLE OF TMEM167 DURING CEREBRAL CORTICOGENESIS

The cerebral cortex controls higher-order functions such as movement, sensory perception, and cognition, and its development relies on tightly regulated neurogenesis and high levels of protein synthesis. During corticogenesis, glutamatergic projection neurons and GABAergic interneurons are generated sequentially from distinct progenitor populations within the forebrain germinal zones. The secretory pathway is a highly conserved process; however, its complexity increases through evolution to meet rising protein demands. Membrane and secretory proteins are transported from the endoplasmic reticulum (ER) to the Golgi apparatus, where they are sorted according to their final destination. Neurons exhibit a unique morphology that makes them particularly sensitive to disruptions in ER-to-Golgi trafficking (Wang et al., 2020). TMEM167A is a ubiquitously expressed Golgi-resident transmembrane protein whose function remains largely unknown, although it is presumed to play a role in ER-to-Golgi transport. Mutations in this gene are associated with severe neurodevelopmental disorders, including microcephaly, lissencephaly, and epilepsy. To better understand the role of TMEM167A during corticogenesis, we investigated the effects of TMEM167A knockdown in the developing mouse cortex using in utero electroporation. Analysis of cortical progenitor cell cycle dynamics, survival, cellular diversity, and projection neuron migration reveals that TMEM167A downregulation alters cell cycle kinetics and delays neuronal migration independently of cell fate.