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: 3.64). 04/2008; 315(2):521-34. DOI: 10.1016/j.ydbio.2007.12.017
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Tiffany A Cook, Jul 30, 2015
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 2.04 Impact Factor
  • Source
    • "For examples, these factors are expressed in photosensitive cells in a wide array of organisms and are critical to guide proper neural/eye specification and photoreceptor development (Finkelstein et al., 1990; Vandendries et al., 1996; Chen et al., 1997; Furukawa et al., 1997; Stornaiuolo et al., 1998; Umesono et al., 1999; Martinez- Morales et al., 2001; Salo et al., 2002; Lanjuin et al., 2003; Nishida et al., 2003; Plouhinec et al., 2003; Koike et al., 2007; Ward et al., 2008; Steinmetz et al., 2010; Passamaneck et al., 2011). High throughput techniques also show that Otd, OTX2 and CRX each regulate several common photoreceptor-specific genes (Ranade et al., 2008; Corbo et al., 2010; Mishra et al., 2010; Omori et al., 2011). Importantly, we find that all three Otd-related factors can largely rescue rhabdomeric morphogenesis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Otd-related transcription factors are evolutionarily conserved to control anterior patterning and neurogenesis. In humans, two such factors, OTX2 and CRX, are expressed in all photoreceptors from early specification through adulthood and associate with several photoreceptor-specific retinopathies. It is not well understood how these factors function independently vs. redundantly, or how specific mutations lead to different disease outcomes. It is also unclear how OTX1 and OTX2 functionally overlap during other aspects of neurogenesis and ocular development. Drosophila encodes a single Otd factor that has multiple functions during eye development. Using the Drosophila eye as a model, we tested the ability of the human OTX1, OTX2, and CRX genes, as well as several disease-associated CRX alleles, to rescue the different functions of Otd. Our results indicate the following: OTX2 and CRX display overlapping, yet distinct subfunctions of Otd during photoreceptor differentiation; CRX disease alleles can be functionally distinguished based on their rescue properties; and all three factors are able to rescue rhabdomeric photoreceptor morphogenesis. Our findings have important implications for understanding how Otx proteins have subfunctionalized during evolution, and cement Drosophila as an effective tool to unravel the molecular bases of photoreceptor pathogenesis.
    Developmental Dynamics 01/2012; 241(1):215-28. DOI:10.1002/dvdy.22782 · 2.67 Impact Factor
  • Source
    • "The transcription factors encoded by otd, or crx and otx2 directly activate the cis-regulatory control systems of the genes encoding the photoreceptor pigments, in flies and mice. In addition the targets of these regulatory genes, in both flies and mice, include phototransduction genes (rhodopsins, transducins, phosphodiesterase genes, arrestins), and cell morphogenesis genes (Ranade et al., 2008). The mammalian Box IV crx/otx2 GRN includes a canonical set of six other regulatory genes, interactions among which in mammals determines the photoreceptor subtype (Hennig et al., 2008; Swaroop et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Evolutionary change in animal morphology results from alteration of the functional organization of the gene regulatory networks (GRNs) that control development of the body plan. A major mechanism of evolutionary change in GRN structure is alteration of cis-regulatory modules that determine regulatory gene expression. Here we consider the causes and consequences of GRN evolution. Although some GRN subcircuits are of great antiquity, other aspects are highly flexible and thus in any given genome more recent. This mosaic view of the evolution of GRN structure explains major aspects of evolutionary process, such as hierarchical phylogeny and discontinuities of paleontological change.
    Cell 03/2011; 144(6):970-85. DOI:10.1016/j.cell.2011.02.017 · 33.12 Impact Factor
Show more