Potential Role of JAK-STAT Signaling Pathway in the Neurogenic-to-Gliogenic Shift in Down Syndrome Brain

Figure 4

Crosstalk between Wnt, Notch, and JAK-STAT signaling pathways. Wnt signaling activates Ngn1, which then binds p300/CBP coactivator proteins to promote neuronal differentiation. Ngn1 competes with STAT3 to inhibit gliogenesis during neurogenic phases. During gliogenesis, the STAT3 transcription factor is activated through phosphorylation by JAKs. The active form of STAT3 binds the p300/CBP coactivator proteins and promotes gliogenesis. Notch signaling activates gliogenic genes; HES inhibits neurogenesis via inhibition of proneural genes. At the same time, RBP-Jκ is also activated to promote gliogenesis. RBP-Jκ binds a repressive cofactor protein, termed nuclear receptor corepressor, to suppress gliogenic genes and inhibit glial cell differentiation when the JAK-STAT pathway is not activated.