The anti-apoptotic role of Mcl-1 during early nervous system development

Abstract

Developmental neurogenesis, the formation of neurons in utero, is tightly regulated by apoptosis, a form of programmed cell death. The pro-survival protein Mcl-1 has been shown to be important for the survival of the developing nervous system through its ability to inhibit apoptosis. This dependency is poorly understood. Moreover, how Mcl-1 inhibits apoptosis in the developing nervous system is unknown. Here, conditional ablation of mcl-1 in the murine developing nervous system (Mcl-1 CKO) resulted in widespread death throughout the developing nervous system. Mcl-1 CKOs showed a progression of apoptosis that mirrors the progression of differentiation in the brainstem and spinal cord. Apoptosis was rescued by co-deleting pro-apoptotic Bax in Mcl-1 CKO mice, demonstrating that Mcl-1 promotes cell survival by blocking the activation of Bax. This work is the first to demonstrate widespread dependency on Mcl-1 during early nervous system development.