Figure 1.

The interactions of Sox and bHLH genes in HC differentiation in mice. Experimental data indicate a complex interaction of Sox and bHLH genes in the progression of HC fate commitment and differentiation. (A) Sox2 and Myc genes act downstream of Eya1/Six1 and are essential for proliferation of HC precursor cells to ensure self-renewal of precursors but also commitment to the HC lineage. These precursor genes are turned off in the neurosensory lineage and bHLH genes are activated that antagonizes Sox2. (B) bHLH TFs can form complex interactions in a given cell that can undergo periodic changes in expression levels and their signal can undergo context dependent variation between gene expression and suppression. Data in mice and flies suggest that all proneural TFs compete for the E-proteins (Tcf3,4,12) to form heterodimers for proper binding. Thus, the level of all proneuronal bHLH TFs (here Atoh1 and Neurod1) and available E-proteins as well as their binding preference will determine how much signaling of heterodimers will occur. Importantly, E-proteins can also interact with Hes/Hey factors and the inhibitors of DNA binding (Ids), limiting availability of E-proteins for heterodimerization of proneuronal protein, proportionally to the affinity and concentration of all these interactive partners. In essence, the binding properties and frequency of the binding partners will determine whether a cell is differentiating as a neuron/HC, a supporting/glial cell, or is continuing proliferation as a prosensory precursor. HC, hair cell; SC, supporting cell. Modified after (Fritzsch et al., 2015a).