Increased neuron density in the midbrain of a foveate bird, pigeon, results from profound change in tissue morphogenesis.

The increase of brain neuron number in relation with brain size is currently considered to be the major evolutionary path to high cognitive power in amniotes. However, how changes in neuron density did contribute to the evolution of the information-processing capacity of the brain remains unanswered. High neuron densities are seen as the main reason why the fovea located at the visual center of the retina is responsible for sharp vision in birds and primates.

A transient decrease in mitochondrial activity contributes to establish the ganglion cell fate in retina adapted for high acuity vision.

Although the plan of the retina is well conserved in vertebrates, there are considerable variations in cell type diversity and number, as well as in the organization and properties of the tissue. The high ratios of retinal ganglion cells (RGCs) to cones in primate fovea and bird retinas favor neural circuits essential for high visual acuity and color vision. The role that cell metabolism could play in cell fate decision during embryonic development of the nervous system is still largely unknown.

Delayed neurogenesis with respect to eye growth shapes the pigeon retina for high visual acuity.

The macula and fovea located at the optical centre of the retina make primate visual perception unique among mammals. Our current understanding of retina ontogenesis is primarily based on animal models having no macula and no fovea. However, the pigeon retina and the human macula share a number of structural and functional properties that justify introducing the former as a new model system for retina development.

A positive feedback loop between ATOH7 and a Notch effector regulates cell-cycle progression and neurogenesis in the retina.

The HES proteins are known Notch effectors and have long been recognized as important in inhibiting neuronal differentiation. However, the roles that they play in the specification of neuronal fate remain largely unknown. Here, we show that in the differentiating retinal epithelium, the proneural protein ATOH7 (ATH5) is required for the activation of the transcription of the Hes5.

Conserved regulatory sequences in Atoh7 mediate non-conserved regulatory responses in retina ontogenesis.

The characterisation of interspecies differences in gene regulation is crucial to understanding the molecular basis of phenotypic diversity and evolution. The atonal homologue Atoh7 participates in the ontogenesis of the vertebrate retina. Our study reveals how evolutionarily conserved, non-coding DNA sequences mediate both the conserved and the species-specific transcriptional features of the Atoh7 gene.

Highly conserved sequences mediate the dynamic interplay of basic helix-loop-helix proteins regulating retinogenesis.

The atonal homolog 5 (ATH5) protein is central to the transcriptional network regulating the specification of retinal ganglion cells, and its expression comes under the spatiotemporal control of several basic helix-loop-helix (bHLH) proteins in the course of retina development. Monitoring the in vivo occupancy of the ATH5 promoter by the ATH5, Ngn2, and NeuroM proteins and analyzing the DNA motifs they bind, we show that three evolutionarily conserved E-boxes are required for the bHLH proteins to control the different phases of ATH5 expression. E-box 4 mediates the activity of Ngn2, ATH5, and NeuroM along the pathway leading to the conversion of progenitors into newborn neurons.

The basic domain of ATH5 mediates neuron-specific promoter activity during retina development.

In the developing retina, the gene encoding the beta3 subunit of the neuronal nicotinic receptor, a specific marker of retinal ganglion cells, is under the direct control of the atonal homolog 5 (ATH5) basic helix-loop-helix (bHLH) transcription factor. Although quite short (143 bp in length), the beta3 promoter has the remarkable capacity to discriminate between ATH5 and the other neuronal bHLH proteins expressed in the developing nervous system. We have identified three amino acids within the basic domain that confer specificity to the ATH5 protein.

A bHLH transcriptional network regulating the specification of retinal ganglion cells.

In the developing retina, the production of ganglion cells is dependent on the proneural proteins NGN2 and ATH5, whose activities define stages along the pathway converting progenitors into newborn neurons. Crossregulatory interactions between NGN2, ATH5 and HES1 maintain the uncommitted status of ATH5-expressing cells during progenitor patterning, and later on regulate the transition from competence to cell fate commitment. Prior to exiting the cell cycle, a subset of progenitors is selected from the pool of ATH5-expressing cells to go through a crucial step in the acquisition of a definitive retinal ganglion cell fate.