Plag1 and Plagl2 have overlapping and distinct functions in telencephalic development

摘要

ThePlaggene family has three members;Plagl1/Zac1, which is a tumor suppressor gene, andPlag1andPlagl2, which are proto-oncogenes. All three genes are known to be expressed in embryonic neural progenitors, andZac1regulates proliferation, neuronal differentiation and migration in the developing neocortex. Here we examined the functions ofPlag1andPlagl2in neocortical development. We first attempted, and were unable to generate, E12.5Plag1;Plagl2double mutants, indicating that at least onePlag1orPlagl2gene copy is required for embryonic survival. We therefore focused on single mutants, revealing a telencephalic patterning defect in E12.5Plagl2mutants and a proliferation/differentiation defect inPlag1mutant neocortices. Specifically, the ventral pallium, a dorsal telencephalic territory, expands into the ventral telencephalon inPlagl2mutants. In contrast,Plag1mutants develop normal regional territories, but neocortical progenitors proliferate less and instead produce more neurons. Finally, in gain-of-function studies, bothPlag1andPlagl2reduce neurogenesis and increase BrdU-uptake, indicative of enhanced proliferation, but whilePlagl2effects on proliferation are more immediate,Plag1effects are delayed. Taken together, we found that thePlagproto-oncogenes genes are essential regulators of neocortical development and althoughPlag1andPlagl2functions are similar, they do not entirely overlap.This article has an associated First Person interview with the first author of the paper.