Daughterless homodimer synergizes with Eyeless to induce Atonal expression and retinal neuron differentiation

Abstract

Class I Basic Helix-Loop-Helix (bHLH) transcription factors form homodimers or heterodimers with class II bHLH proteins. While bHLH heterodimers are known to have diverse roles, little is known about the role of class I homodimers. In this manuscript, we show that linked a dimer of Daughterless (Da), the only Drosophila class I bHLH protein, activates Atonal (Ato) expression and retinal neuron differentiation synergistically with the retinal determination factor Eyeless (Ey). The HLH protein Extramacrocheate (Emc), which forms heterodimer with Da, antagonizes the synergistic activation from Da but not the Da-Da linked dimer with Ey. We show that Da directly interacts with Ey and promotes Ey binding to the Ey binding site in the Ato 3′ enhancer. Interestingly, the Ey binding site in the Ato 3′ enhancer contains an embedded E-box that is also required for the synergistic activation by Ey and Da. Finally we show that mammalian homologs of Ey and Da can functionally replace their Drosophila counterparts to synergistically activate the Ato enhancer, suggesting that the observed function is evolutionary conserved.

Type I bHLH Proteins Daughterless and Tcf4 Restrict Neurite Branching and Synapse Formation by Repressing Neurexin in Postmitotic Neurons

“…Therefore, we hypothesized that Da homodimers would mimic the phenotypes we observe with Da overexpression alone. Recently, peptide-linked Da homodimers were created and can be expressed in a tissue specific fashion using Gal4/UAS (Tanaka-Matakatsu et al, 2014). We expressed these homodimers specifically in postmitotic neurons and analyzed their effect on axon arborization at the Drosophila NMJ.…”

“…Generally, class I bHLH proteins heterodimerize with class II bHLH proteins to activate gene expression (Powell and Jarman, 2008). However, class I bHLH proteins have also been reported to homodimerize (Cabrera and Alonso, 1991), and restrict (Lim et al, 2008) or activate (Tanaka-Matakatsu et al, 2014) gene expression. Class I bHLH proteins also form heterodimers with class V bHLH proteins of the Inhibitor of Differentiation (ID) family.…”

Distinct regulation of atonal in a visual organ of Drosophila : Organ-specific enhancer and lack of autoregulation in the larval eye

“…ato Dep =ato-dependent, maintenance phase; ato Ind =ato-independent, initiation phase. References: 1=Sun et al 1999; 2=Zhang et al, 2006; 3=Zhou et al, 2016; 4=Tanaka-Matakatsu and Du., 2008; 5=Tanaka-Matakatsu et al, 2014; 6=Zhou et al, 2014; 7=zur Lage et al, 2004; 8=Sprecher et al, 2007. (D–D′) Visualization of the BO during embryonic development.…”

ESCRT-0 complex modulates Rbf mutant cell survival by regulating Rhomboid endosomal trafficking and EGFR signaling

“…Anterior to the morphogenetic furrow, cells are undifferentiated and asynchronously proliferating. Expression of Ato, which is induced by retinal determination factors and bHLH protein Daughterless just anterior to the morphogenetic furrow (Tanaka-Matakatsu and Du, 2008;Tanaka-Matakatsu et al, 2014Zhang et al, 2006), is progressively restricted to small clusters and eventually to the individual R8 precursors within the morphogenetic furrow (Sun et al, 1998). The R8 precursors express the membrane protease Rhomboid (Rho) and release EGFR ligands to activate EGFR signaling, which regulates stepwise retinal differentiation and cell proliferation, and promotes cell survival in posterior eye discs (Baker and Yu, 2001;Dominguez et al, 1998).…”