Figure 4.

bHLH transcription factors are regulated by a variety of signaling pathways: Notch, BMP, Wnt, and FGF signaling. (A) Proneural transcription factors induce the expression Dll1 ligand in the emitting cell (right). Dll1 ligand binds to the Notch1 receptor on the receiving cell (left), which causes the NICD to be cleaved and translocated to the nucleus. After translocation to the nucleus, NICD interacts with CSL to initiate the transcription of Hes1, which inhibits the expression of proneural genes. (B) BMP ligand binds to serine-threonine kinase receptors, BMP receptors, which initiate the expression of Neurog2 and repress the expression of Oilg1/2 through activation of ID2/4. Simultaneously, Ascl1 and Atoh1 are broken down by proteolysis. (C) Interaction of Wnt with the transmembrane receptor, frizzled (FZ) and low-density lipoprotein receptor (LRP) activates disheveled (DVL), which can induce the release of β-catenin from the β-catenin destruction complex (stabilization). After the stabilization of β-catenin, it translocates to the nucleus to initiate the expression of numerous bHLH genes. (D) FGF ligand binds to receptor tyrosine kinase (RTK) to induce dimerization which activates RAS, RAF, MEK, and ERK signaling. These signaling cascades induce the expression of Ascl1 and repress the expression of Neurog2.