Pph13 and Orthodenticle define a dual regulatory pathway for photoreceptor cell morphogenesis and function

Mishra, Monalisa; Oke, Ashwini; Lebel, Cindy; McDonald, Elizabeth C.; Plummer, Zachary; Cook, Tiffany; Zelhof, Andrew C.

doi:10.1242/jcs079244

Cited by 10 publications

(25 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These genes are expressed in a photoreceptor subtype-specific manner (Tahayato et al, 2003), and their expression patterns can be recapitulated using <500 bp regulatory sequence located directly upstream of the TATA box (Fortini and Rubin, 1990; Papatsenko et al, 2001; Tahayato et al, 2003; Zuker et al, 1985). Recent studies have demonstrated that many of the same factors that are necessary for controlling Rh3 - Rh6 gene expression in vivo also properly regulate Rh promoter activity in cultured Drosophila S2 cells (Xie et al, 2007; Mishra et al, 2010). Otd, for instance, is critical for Rh3 and Rh5 expression in vivo , and activates the Rh3 and Rh5 promoters in vitro (Fig 2) (Xie et al, 2007).…”

Section: Resultsmentioning

confidence: 99%

“…Otd, for instance, is critical for Rh3 and Rh5 expression in vivo , and activates the Rh3 and Rh5 promoters in vitro (Fig 2) (Xie et al, 2007). Interestingly, although Otd represses Rh6 in OPRs in vivo , Otd weakly activates the Rh6 promoter alone and synergistically activates Rh6 with Senseless (Sens) in vitro (Mishra et al, 2010; Tahayato et al, 2003; Xie et al, 2007). Since Sens is restricted to R8 photoreceptors and is required for Rh6 expression , but does not bind directly to the Rh6 promoter sequence, these in vitro experiments provide evidence that Sens is involved in activating Rh6 expression by interacting with Otd, and reveal that Otd may activate or repress Rh6 in different PR subtypes.…”

Section: Resultsmentioning

confidence: 99%

“…Morphologically, control outer photoreceptor (OPR) rhabdomeric membranes span the entire depth of the retina (~100 μm) (Fig 3D), and their actin-rich surfaces, recognized by fluorescently-labeled phalloidin, form highly regular, trapezoidal arrangement surrounding the smaller rhabdomere of the R7 (or R8) (Fig 3E). In contrast, OPR rhabdomeres in otd uvi flies fail to extend more than 1/3 the depth of the retina (Fig 3H), and these rhabdomeres fail to form properly (Mishra et al, 2010; Tahayato et al, 2003; Vandendries et al, 1996), making individual rhabdomeres difficult to visualize with phalloidin (Fig 3I). Similar to control flies, OtdFL rescues develop fully-elongated and organized rhabdomeres (Fig 3L, M).…”

Section: Resultsmentioning

confidence: 99%

“…However, it remains possible that Otd’s C-terminus is also important for regulating additional targets involved in protein trafficking. Indeed, recent microarray studies of otd uvi mutants have uncovered several such candidates (Mishra et al, 2010; Ranade et al, 2008). Thus, further analysis of other Otd target genes with the different Otd deletions may be informative for better understanding the likely complex role of Otd in regulating photoreceptor morphogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…While Otd does not appear to affect early photoreceptor specification, many aspects of PR terminal differentiation are Otd-dependent. For instance, during mid-pupation, Otd is necessary for proper rhabdomere morphogenesis in all PRs, and later during pupation and in adulthood, Otd activates Rh3 and Rh5 in pale IPRs, and represses Rh6 in OPRs (Mishra et al, 2010; Tahayato et al, 2003; Vandendries et al, 1996). …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events

McDonald

Xie

Workman

et al. 2010

Developmental Biology

Self Cite

View full text Add to dashboard Cite

Summary Orthodenticle (Otd)-related transcription factors are essential for anterior patterning and brain morphogenesis from Cnidaria to Mammals, and genetically underlie several human retinal pathologies. Despite their key developmental functions, relatively little is known regarding the molecular basis of how these factors regulate downstream effectors in a cell- or tissue-specific manner. Many invertebrate and vertebrate species encode two to three Otd proteins, whereas Drosophila encodes a single Otd protein. In the fly retina, Otd controls rhabdomere morphogenesis of all photoreceptors and regulates distinct Rhodopsin-encoding genes in a photoreceptor subtype-specific manner. Here, we performed a structure-function analysis of Otd during Drosophila eye development using in vivo rescue experiments and in vitro transcriptional regulatory assays. Our findings indicate that Otd requires at least three distinct transcriptional regulatory domains to control photoreceptor-specific rhodopsin gene expression and photoreceptor morphogenesis. Our results also uncover a previously unknown role for Otd in preventing co-expression of sensory receptors in blue vs. green-sensitive R8 photoreceptors. Sequence analysis indicates that many of the transcriptional regulatory domains identified here are conserved in multiple Diptera Otd-related proteins. Thus, these studies provide a basis for identifying shared molecular pathways involved in a wide range of developmental processes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events

McDonald

Xie

Workman

et al. 2010

Developmental Biology

Self Cite

View full text Add to dashboard Cite

show abstract

The power of the (imperfect) palindrome: Sequence‐specific roles of palindromic motifs in gene regulation

Datta

Rister

2022

BioEssays

View full text Add to dashboard Cite

In human languages, a palindrome reads the same forward as backward (e.g., 'madam').In regulatory DNA, a palindrome is an inverted sequence repeat that allows a transcription factor to bind as a homodimer or as a heterodimer with another type of transcription factor. Regulatory palindromes are typically imperfect, that is, the repeated sequences differ in at least one base pair, but the functional significance of this asymmetry remains poorly understood. Here, we review the use of imperfect palindromes in Drosophila photoreceptor differentiation and mammalian steroid receptor signaling. Moreover, we discuss mechanistic explanations for the predominance of imperfect palindromes over perfect palindromes in these two gene regulatory contexts. Lastly, we propose to elucidate whether specific imperfectly palindromic variants have specific regulatory functions in steroid receptor signaling and whether such variants can help predict transcriptional outcomes as well as the response of individual patients to drug treatments.

show abstract

The retinal mosaics of opsin expression in invertebrates and vertebrates

Rister

Desplan

2011

Developmental Neurobiology

View full text Add to dashboard Cite

Colour vision is found in many invertebrate and vertebrate species. It is the ability to discriminate objects based on the wavelength of emitted light independent of intensity. As it requires the comparison of at least two photoreceptor types with different spectral sensitivities, this process is often mediated by a mosaic made of several photoreceptor types. In this review, we summarize the current knowledge about the formation of retinal mosaics and the regulation of photopigment (opsin) expression in the fly, mouse and human retina. Despite distinct evolutionary origins, as well as major differences in morphology and phototransduction machineries, there are significant similarities in the stepwise cell-fate decisions that lead from progenitor cells to terminally differentiated photoreceptors that express a particular opsin. Common themes include i) the use of binary transcriptional switches that distinguish classes of photoreceptors, ii) the use of gradients of signaling molecules for regional specializations, iii) stochastic choices that pattern the retina and iv) the use of permissive factors with multiple roles in different photoreceptor types.

show abstract

Pph13 and Orthodenticle define a dual regulatory pathway for photoreceptor cell morphogenesis and function

Cited by 10 publications

References 1 publication

Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events

Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events

The power of the (imperfect) palindrome: Sequence‐specific roles of palindromic motifs in gene regulation

The retinal mosaics of opsin expression in invertebrates and vertebrates

Contact Info

Product

Resources

About