['All vertebrate peripheral nerves connect the central nervous system (CNS) with targets in the periphery and are composed of axons, layers of ensheathing glia and connective tissue. Although the structure of these conduits is well established, very little is known about the origin and developmental roles of some of their elements. One understudied component, the perineurium, ensheaths nerve fascicles and is a component of the blood-nerve-barrier. In zebrafish, the motor nerve perineurium is composed of CNS-derived nkx2.2a(+) perineurial glia, which establish the motor exit point (MEP) during development. To determine if mouse perineurial cells also originate within the CNS and perform a similar function, we created a Nkx2.2:EGFP transgenic reporter line.', 'In conjunction with RNA expression analysis and antibody labeling, we observed Nkx2.2(+) cells along peripheral motor nerves at all stages of development and in adult tissue. Additionally, in mice lacking Nkx2.2, we demonstrate that Nkx2.2(+) perineurial glia are essential for motor nerve development and Schwann cell differentiation.'] Do mammalian Nkx2.2+ perineurial glia are essential for motor nerve development?