Relevance to Autism

Fiddes et al., 2018 demonstrated that different alleles of the human-specific NOTCH2NL gene were expressed in radial glia and had varying potencies in enhancing Notch signaling via direct interaction with NOTCH receptors; consistent with a role in Notch signaling, overexpression of NOTCH2NL delayed neuronal differentiation, whereas deletion accelerated it. Furthermore, two alleles of the NOTCH2NL gene (NOTCH2NLA and NOTCH2NLB) were found in this report to serve as breakpoints in 1q21.1 deletion/duplication syndrome.

Molecular Function

Human-specific protein that promotes neural progenitor proliferation and evolutionary expansion of the brain neocortex by regulating the Notch signaling pathway. Able to promote neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thereby delaying the differentiation of neuronal progenitors and leading to an overall final increase in neuronal production. Acts by enhancing the Notch signaling pathway via two different mechanisms that probably work in parallel to reach the same effect: enhances Notch signaling pathway in a non-cell-autonomous manner via direct interaction with NOTCH2, and also promotes Notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, which promotes neuronal differentiation.

External Links

References