Ebf2 Marks Early Cortical Neurogenesis and Regulates the Generation of Cajal-Retzius Neurons in the Developing Cerebral Cortex

Mammalian cortical neurogenesis occurs on a precise time schedule during development. The earliest born neurons form the preplate and later separate into layer 1, which includes Cajal-Retzius (C-R) neurons, and the subplate. The preplate and its derivatives play a critical role in regulating subsequent neuron migration and cortical lamination. Using an early B cell factor 2 (Ebf2)-enhanced green fluorescent protein (EGFP) transgenic mouse line, we show that Ebf2-EGFP is expressed in the preplate and persists in C-R neurons, allowing us to follow the development of these early born neurons. Therefore, Ebf2 is a genetic marker for preplate neurons from the earliest stage of their differentiation and C-R cells after the preplate is split. Additionally, we examined the function of Ebf2 in the development of C-R neurons using both lentiviral-mediated knock-down overexpression approaches to perturb Ebf2 expression. Our data show that Ebf2 overexpression increases the generation of early born neurons including C-R cells, while Ebf2 knock-down decreases it, without affecting the generation of other layer-specific neurons in vitro. These results indicate that Ebf2 is important for early cortical neurogenesis and regulates the generation of C-R neurons in the developing cerebral cortex.