Analysis of the Otd-dependent transcriptome supports the evolutionary conservation of CRX/OTX/OTD functions in flies and vertebrates

Department of Ophthalmology, Harvard Medical School and the Massachusetts Eye and Ear Infirmary, 243 Charles Street MEEI 507, Boston, MA 02445, USA.
Developmental Biology (Impact Factor: 3.55). 04/2008; 315(2):521-34. DOI: 10.1016/j.ydbio.2007.12.017
Source: PubMed


Homeobox transcription factors of the vertebrate CRX/OTX family play critical roles in photoreceptor neurons, the rostral brain and circadian processes. In mouse, the three related proteins, CRX, OTX1, and OTX2, fulfill these functions. In Drosophila, the single founding member of this gene family, called orthodenticle (otd), is required during embryonic brain and photoreceptor neuron development. We have used global gene expression analysis in late pupal heads to better characterize the post-embryonic functions of Otd in Drosophila. We have identified 61 genes that are differentially expressed between wild type and a viable eye-specific otd mutant allele. Among them, about one-third represent potentially direct targets of Otd based on their association with evolutionarily conserved Otd-binding sequences. The spectrum of biological functions associated with these gene targets establishes Otd as a critical regulator of photoreceptor morphology and phototransduction, as well as suggests its involvement in circadian processes. Together with the well-documented role of otd in embryonic patterning, this evidence shows that vertebrate and fly genes contribute to analogous biological processes, notwithstanding the significant divergence of the underlying genetic pathways. Our findings underscore the common evolutionary history of photoperception-based functions in vertebrates and invertebrates and support the view that a complex nervous system was already present in the last common ancestor of all bilateria.

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    • "However, as for the spalt locus in the R8 photoreceptor neuron, so far Orthodenticle does not appear to play any role in early cell fate commitment (Fichelson et al., 2012; Vandendries et al., 1996). Instead, it is required later during photoreceptor pupal development to promote the timely remodeling of the apico-basal axis of the cell and rhabdomere elongation (Fichelson et al., 2012; Mishra et al., 2010; Ranade et al., 2008). Part of Orthodenticle's function here is to repress the expression of kruppel-h1, which encodes a member of the conserved Kruppel-like Zn-finger transcription factor family (Fichelson et al., 2012). "
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    ABSTRACT: Understanding how a functional organ can be produced from a small group of cells remains an outstanding question in cell and developmental biology. The developing compound eye of Drosophila has long been a model of choice for addressing this question by dissecting the cellular, genetic and molecular pathways that govern cell specification, differentiation, and multicellular patterning during organogenesis. In this review, I focus on cell and tissue morphogenesis during fly retinal development, including the regulated changes in cell shape and cell packing that ultimately determine the shape and architecture of the compound eye. In particular, I review recent studies that highlight the prominent roles of transcriptional and hormonal controls that orchestrate the cell shape changes, cell-cell junction remodeling and polarized membrane growth that underlie photoreceptor morphogenesis and retinal patterning.
    Developmental Biology 10/2013; 385(2). DOI:10.1016/j.ydbio.2013.09.031 · 3.55 Impact Factor
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    • "Consistent with their origin from the ocular segment, these adult visual structures express the otd gene during their development. Thus, Otd is expressed in all of the developing photoreceptors of the compound eyes (and the Hofbauer–Buchner eyelet [38,44–46]). In the compound eye photoreceptors, otd is required for proper rhabdomere formation, as well as for the correct expression of Rh3, Rh5 and Rh6 rhodopsins (figure 2c) [46–48]. "
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    ABSTRACT: The regional specialization of brain function has been well documented in the mouse and fruitfly. The expression of regulatory factors in specific regions of the brain during development suggests that they function to establish or maintain this specialization. Here, we focus on two such factors-the Drosophila cephalic gap genes empty spiracles (ems) and orthodenticle (otd), and their vertebrate homologues Emx1/2 and Otx1/2-and review novel insight into their multiple crucial roles in the formation of complex sensory systems. While the early requirement of these genes in specification of the neuroectoderm has been discussed previously, here we consider more recent studies that elucidate the later functions of these genes in sensory system formation in vertebrates and invertebrates. These new studies show that the ems and Emx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective olfactory systems. Moreover, they demonstrate that the otd and Otx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective visual systems. Based on these recent experimental findings, we discuss the possibility that the olfactory and visual systems of flies and mice share a common evolutionary origin, in that the conserved visual and olfactory circuit elements derive from conserved domains of otd/Otx and ems/Emx action in the urbilaterian ancestor.
    Open Biology 05/2013; 3(5):120177. DOI:10.1098/rsob.120177 · 5.78 Impact Factor
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    • "This interpretation can be biased because all these cases are related to Hox genes. However, members of other families of transcription factors such as otd, Krüppel (Kr), and tailless (tll) are involved in conserved aspects of nervous system development throughout metazoans, and their segmentation roles might be restricted to arthropods or to some groups of arthropods (Gui et al., 2011; Janssen et al., 2011; Ranade et al., 2008). "
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    ABSTRACT: The fruit fly Drosophila melanogaster is a great model system in developmental biology studies and related disciplines. In a historical perspective, I focus on the formation of the Drosophila segmental body plan using a comparative approach. I highlight the evolutionary trend of increasing complexity of the molecular segmentation network in arthropods that resulted in an incredible degree of complexity at the gap gene level in derived Diptera. There is growing evidence that Drosophila is a highly derived insect, and we are still far from fully understanding the underlying evolutionary mechanisms that led to its complexity. In addition, recent data have altered how we view the transcriptional regulatory mechanisms that control segmentation in Drosophila. However, these observations are not all bad news for the field. Instead, they stimulate further study of segmentation in Drosophila and in other species as well. To me, these seemingly new Drosophila paradigms are very challenging ones.
    genesis 08/2012; 50(8):585-98. DOI:10.1002/dvg.22019 · 2.02 Impact Factor
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