Specification of neurotransmitter receptor identity in developing retina: the chick ATH5 promoter integrates the positive and negative effects of several bHLH proteins

Abstract

Genetic studies in Drosophila and in vertebrates have implicated basic helix-loop-helix (bHLH) transcription factors in neural determination and differentiation. In this report, we analyze the role that several bHLH proteins play in the transcriptional control of differentiation in chick retina. Our experimental system exploits the properties of the promoter for the beta 3 subunit of the neuronal acetylcholine receptors, important components of various phenotypes in the CNS of vertebrates. The beta 3 subunit contributes to define ganglion cell identity in retina and its promoter, whose activation is an early marker of ganglion cell differentiation, is under the specific control of the chick atonal homolog ATH5. Functional analysis of the ATH5 promoter indicates that interactions between ATH5 and several other bHLH transcription factors underlie the patterning of the early retinal neuroepithelium and form a regulatory cascade leading to transcription of the gene for beta 3. ATH5 appears to coordinate the transcriptional pathways that control pan-neuronal properties with those that regulate the subtype-specific features of retinal neurons.

Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development

“…Multiple lines of evidence from this study suggest that the gene regulatory networks controlling photoreceptor development differ substantially between mice and humans. We identified ATOH7 expression in late-stage neurogenic RPCs, amacrine-horizontal cell precursors, bipolar-photoreceptor precursors and immature photoreceptors, in addition to its expression in early-stage neurogenic RPCs, which has been observed in other species (Figures 7A, S7A, and S7B;Brown et al, 1998;Kanekar et al, 1997;Kay et al, 2001;Matter-Sadzinski et al, 2001). ATOH7 expression in immature photoreceptors was confirmed using immunostaining for ATOH7 and the early photoreceptor-enriched markers OTX2 and CRX.…”

A screen for downstream effectors of Neurogenin2 in the embryonic neocortex

“…The demonstration that the expression of pan-neuronal markers, and hence neurogenesis, is regulated by proneural genes is not surprising given the known requirement for proneural genes to function as neural determination genes (Bertrand et al, 2002;Schuurmans and Guillemot, 2002). At the same time, several neuronal subtype markers, including b3-AChR, L7, mGluR6, VGLUT1/2, GluR2, GAD1/2, and Xomp2, have been shown to be regulated by proneural activity in different systems (Burns and Vetter, 2002;Fode et al, 2000;Lo et al, 1998;Matter-Sadzinski et al, 2001;Schuurmans et al, 2004;Tomita et al, 2000). This is consistent with the known role of proneural genes in specifying neuronal subtype identities in both fly and mammals (Fode et al, 2000;Jarman et al, 1993;Lo et al, 2002;Parras et al, 2002).…”

Increased neuron density in the midbrain of foveate birds results from profound change in tissue morphogenesis

“…However, while transcript level reached a plateau in chicken at E12, it was still increasing in pigeon at E15. NeuroD1 is a regulator of neuron differentiation in the avian nervous system (Matter-Sadzinski et al, 2001; Roztocil et al, 1997) and the expression patterns of this gene were similar in pigeon and chicken until E12. Then, NeuroD1 was rapidly downregulated in chicken, whereas, in pigeon, expression was maintained at high levels at least until E15 (Figure 11B), indicating that neuron production was extended over several days.…”