The family consisting of Neurogenin-1, Neurogenin-2, and Neurogenin-3, plays a fundamental role in specifying neural precursor cells and regulating the differentiation of neurons during embryonic development.
Their involvement spans various stages of neurogenesis, including the determination of neural progenitor identity, cell cycle exit, and the acquisition of neuronal characteristics.
[5][6] Neurogenins holds significant implications for clinical research, particularly in the context of neurodevelopmental disorders and neurological regeneration.
[7] Aberrations in the expression or regulation of Neurogenins have been linked to conditions such as autism spectrum disorders and neurodegenerative diseases.
[8] Ongoing research continues to explore the therapeutic potential of manipulating Neurogenin activity for neural repair and regeneration.
[9] Ngn1 is a proneural gene because its expression is seen prior to neural lineage determination, indicating it plays a role in neuronal differentiation.
[10] Activation of the notch pathway, causes the inhibition of proneural bHLH genes, such as Ngn1, which allows for the CBP/p300/Smad1 to interact with STAT1/3 and induce gliogenesis.
[10] Along with the embryonic rat, it was also seen in zebrafish that the repression of Ngn1 by Notch, promotes glial lineage in neural crest and central nervous system formation through the inhibition of neuronal differentiation.
In the absence of Ngn1, the LIF pathway is able to activate STAT1/3, which allows for the promotion of GFAP transcription via the STAT binding site.
This protein binds to enhancer-box regulatory elements on the promoters of many genes related to neurogenesis and neural specification.
This was observed in mice lacking Ngn2 and mash-1 (another proneural bHLH transcription factor), which have more glia in the cortex and decreased capacity to generate neurons.
[17] Heterodimerized Ngn2/enhancer protein complex can bind to enhancer boxes to promote transcription of genes related to a non-specified neuronal fate.
Phosphorylation of Ngn2 enables interaction with LIM-homeodomain proteins, leading to ventral neural fate and motor neuron specification.
Studies have demonstrated that knockout of Ngn3 in mice leads to death shortly after birth possibly due to after effects of severe diabetes.
[19] Further studies are taking place to investigate Ngn3's possible role as a treatment for diabetes and regeneration of cells in the pancreas.
It is important to mention that Ngn3 has three HES1 binding sites adjacent to the TATA box sequence that allow for the regulation of this transcription factor.