A Fly's Eye View of Corneal Development

OBJECTIVES: 1) To understand the interplay between intrinsic transcription factors and extrinsic signals in retinal cell fate determination; 2) To appreciate the role of mechanical forces in shaping apical extracellular matrix structures such as the Drosophila corneal lens; 3) To understand how the Drosophila corneal lens can be used to model human corneal disease. LECTURE SUMMARY: The Drosophila corneal lens is a precisely curved structure made entirely of apical extracellular matrix that resembles the mammalian cornea in its ability to focus light onto the photoreceptors. The non-neuronal cone and pigment cells that secrete the corneal lens differentiate from the same progenitor cells in the eye imaginal disc as the photoreceptors. Photoreceptor differentiation requires a zinc finger transcription factor, Glass. scRNA-Seq data shows that most photoreceptors arrest early in their development in glass mutants, but R8, the first photoreceptor to form in each cluster, is less affected. Similarly, Epidermal Growth Factor Receptor (EGFR) signaling is required for the differentiation of all photoreceptors other than R8. We find that in a heterologous context, Glass and EGFR signaling interact synergistically to induce neuronal gene expression. In addition to its role in photoreceptors, Glass also acts autonomously in the non-neuronal cells of the eye, activating distinct sets of target genes in each cell type. As these cells differentiate, they secrete corneal lens material a...
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