Nkx6.1 enhances neural stem cell activation and attenuates glial scar formation and neuroinflammation in the adult injured spinal cord

Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

“…The Cai lab has identified two neurogenic genes that bind to Notch1 locus in the role of neural differentiation in the developing spinal cord, Nkx6.1 and Gsx1 [ 148 , 149 ]. Studies with Nkx6.1 and Gsx1 both show a decrease in glial scar formation when they are virally overexpressed [ 143 , 150 ]. Nkx6.1 failed to show functional locomotor recover in mice; however, the expression of Gsx1 in ubiquitous NSPCs or Sox2 in NG2+ polydendrocyte NSPC populations resulted in an improved locomotor function after SCI and a reduction in glial scarring [ 143 , 147 ].…”

Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease

“…The activities of Notch pathway and NSPCs can be traced by the reporter GFP expression (Figure 3A). The cell fate of GFP tagged interneuron progenitors have been characterized in both normal development and neurological disease/injury conditions, which facilitate the study of the potentials of NSPCs in regenerative medicine [79][80][81][82]. In these studies, the Cai lab has demonstrated that GFP+ NSPCs preferentially differentiate into interneurons of the brain and spinal cord during embryonic development and in adulthood [56,80].…”

“…Many NSPC subpopulations have been identified, but functional and mechanistic understanding is limited [89]. Transgenic animal models such as the Notch1CR2-GFP allow in vivo investigation of specific NSPC populations and are vital to develop effective therapeutics in the future [56,[79][80][81][82].…”

“…The Notch1CR2-GFP transgenic animal model serves as a valuable tool to study endogenous NSPCs following traumatic CNS injury [56,[79][80][81][82]. Further, NSPCs represent an important cell source for neural regeneration in the adult mammalian CNS [56,[79][80][81][82]. For this reason, diversity of NSPC populations (e.g., Nestin+, Notch1+, NG2+, Foxj1+ cells) have become an intensely focused area of research in regenerative medicine for CNS diseases and injuries.…”

“…Several controversial issues arise and are discussed in the next section. The Notch1CR2-GFP transgenic animal model serves as a valuable tool to study endogenous NSPCs following traumatic CNS injury [56,[79][80][81][82]. Further, NSPCs represent an important cell source for neural regeneration in the adult mammalian CNS [56,[79][80][81][82].…”