Function of pioneer neurons specified by the basic helix-loop-helix transcription factor atonal in neural development

Basic helix-loop-helix (bHLH) transcription factors regulate the differentiation of various tissues in a vast diversity of species. The bHLH protein Atonal was first identified as a proneural gene involved in the formation of mechanosensory cells and photoreceptor cells in Drosophila (Jarman et al., 1993, 1994). Atonal is expressed in sensory organ precursors and is required and sufficient for the development of chordotonal organs (Jar-man et al., 1993). Moreover, Atonal expression is observed in the developing eye and is essential for the differentiation of R8 photoreceptors, which are the first photoreceptors that appear during development. Atonal is not involved in the formation of other photoreceptors (R1–R7) directly. However, R8 photore-ceptors recruit other photoreceptors from the surrounding cells (Jarman et al., 1994). The roles of Atonal as a proneural gene are conserved throughout evolution. In vertebrates, Atonal orthologs are classified into three gene families: neurogenin genes (Neurog1, one of the most closely related human ortho-logs of Atonal is expressed in the progenitors of retinal ganglion cells (RGCs) and is essential for RGC differentiation and retinal development. Atoh7 mutant mice lack optic nerves and have a reduction in the numbers of RGCs, which affects the development of their retinal vasculature (Huang et al., 2014). Highlighting the importance of ATOH7 function in retinal development , mutations of ATOH7 have been identified in populations with congenital diseases of the optic nerve and retinal vascula-ture, such as non-syndromic congenital retinal nonattachment (NCRNA) in the Iranian Kurdish population (Ghiasvand et al., 2011). Individuals with NCRNA lack optic nerves, are totally blind, and have no perception of light. In addition, Atonal-related genes regulate the differentiation of olfactory receptor neurons (ORNs). In Drosophila, Atonal is a proneural gene that acts on a subset of ORNs (Gupta and Rodrigues, 1997). In mammals, a number of bHLH transcription factors, such as Mammalian achaete-scute homologue 1 (Mash1), Neurogenin1, and NeuroD, are required for the differentiation of olfactory sensory neurons (OSNs) (Cau et al., 2002). It is suggested that ORNs specified by Atonal pioneer antennal lobe development in Drosophila. However, the detailed mechanism underlying this process has not yet been fully understood. We recently reported the hierarchical axon targeting of ORNs specified by the bHLH transcription factors Atonal and Amos (Okumura et al., 2016). In Drosophila, ORNs whose cell bodies are located at the sensilla on the surface of antennae and max-illary palps detect odors and send olfactory information to the antennal lobe …