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The male-specific histone variantHTR10 contains ten polymorphicsites/regions compared to canonicalhistone H3.3, most of them conservedin the HTR10 ortholog from closelyrelated species. Some of these sitesmight provide specific functions toHTR10 in the zygote/embryo. If this isthe case, the effect would have to bealmost instantaneous after fertilization,as HTR10 is actively removed fromthe zygote before the first cell division.However, it remains to be determinedwhether zygotic HTR10 removal iscomplete, or whether a small fractionis retained. HTR10 could also affectdevelopment of the endosperm,from which it is only passively lostthrough successive rounds of DNAreplication [5].

Ingouff et al. [9] demonstrate thatthe histone H3 content is severelyrestricted in mature germ cells, andthat replication-dependent H3.1variants appear to be excludedfrom the chromatin. This suggeststhat pre-fertilization histone H3reprogramming in A. thaliana is DNAreplication-independent. Sucha mechanism would release some ofthe temporal constraints of genomereprogramming, giving more flexibilityto the paternal and maternal genomesto reorganize their chromatin.This observation also should helpidentify the histone chaperonecomplex responsible for loading thegamete-specific H3.3 variants.

Interestingly, Ingouff et al. [9] show thatthe Arabidopsis orthologs of HIRA andCHD1 are not implicated in the process,suggesting that an unknown histoneH3.3-loading complex yet to beuncovered exists in plants and actsduring male and female germlinedifferentiation. Recently, a newhistone H3.3-loading complex (deathdomain-associated protein (DAXX))has been discovered in animals [12,13].Although DAXX orthologs are notpresent in A. thaliana, this findingsupports the hypothesis that unknownloading complexes remain to bediscovered.

References1. Slotkin, R.K., Vaughn, M., Borges, F.,

Tanurdzic, M., Becker, J.D., Feijo, J.A., andMartienssen, R.A. (2009). Epigeneticreprogramming and small RNA silencing oftransposable elements in pollen. Cell 136,461–472.

2. Schoft, V.K., Chumak, N., Mosiolek, M.,Slusarz, L., Komnenovic, V., Brownfield, L.,Twell, D., Kakutani, T., and Tamaru, H. (2009).Induction of RNA-directed DNA methylationupon decondensation of constitutiveheterochromatin. EMBO Rep. 10, 1015–1021.

3. Gehring, M., Bubb, K.L., and Henikoff, S. (2009).Extensive demethylation of repetitive elementsduring seed development underlies geneimprinting. Science 324, 1447–1451.

4. Hsieh, T.F., Ibarra, C.A., Silva, P., Zemach, A.,Eshed-Williams, L., Fischer, R.L., andZilberman, D. (2009). Genome-widedemethylation of Arabidopsis endosperm.Science 324, 1451–1454.

5. Ingouff, M., Hamamura, Y., Gourgues, M.,Higashiyama, T., and Berger, F. (2007). Distinctdynamics of HISTONE3 variants between thetwo fertilization products in plants. Curr. Biol.17, 1032–1037.

6. Okada, T., Endo, M., Singh, M.B., andBhalla, P.L. (2005). Analysis of the histone H3

gene family in Arabidopsis and identification ofthe male-gamete-specific variant AtMGH3.Plant J. 44, 557–568.

7. Govin, J., Caron, C., Lestrat, C., Rousseaux, S.,and Khochbin, S. (2004). The role of histones inchromatin remodelling during mammalianspermiogenesis. Eur. J. Biochem. 271,3459–3469.

8. Torres-Padilla, M.E., Bannister, A.J., Hurd, P.J.,Kouzarides, T., and Zernicka-Goetz, M. (2006).Dynamic distribution of the replacementhistone variant H3.3 in the mouse oocyte andpreimplantation embryos. Int. J. Dev. Biol. 50,455–461.

9. Ingouff, M., Berger, F., Holec, S., Lahouze, B.,Xin, N., Foo, S.H., Rademacher, S., �Solji�c, L.,Readshaw, A., and Sprunck, S. (2010). Zygoticresetting of the HISTONE3 variant repertoireparticipates in epigenetic reprogramming inArabidopsis. Curr. Biol. 20, 2137–2143.

10. Hammoud, S.S., Nix, D.A., Zhang, H.,Purwar, J., Carrell, D.T., and Cairns, B.R. (2009).Distinctive chromatin in human spermpackages genes for embryo development.Nature 460, 473–478.

11. Brykczynska, U., Hisano, M., Erkek, S.,Ramos, L., Oakeley, E.J., Roloff, T.C.,Beisel, C., Schubeler, D., Stadler, M.B., andPeters, A.H. (2010). Repressive and activehistone methylation mark distinct promoters inhuman and mouse spermatozoa. Nat. Struct.Mol. Biol. 17, 679–687.

12. Drane, P., Ouararhni, K., Depaux, A.,Shuaib, M., and Hamiche, A. (2010). Thedeath-associated protein DAXX is a novelhistone chaperone involved in thereplication-independent deposition of H3.3.Genes Dev. 24, 1253–1265.

13. Goldberg, A.D., Banaszynski, L.A., Noh, K.M.,Lewis, P.W., Elsaesser, S.J., Stadler, S.,Dewell, S., Law, M., Guo, X., Li, X., et al. (2010).Distinct factors control histone variant H3.3localization at specific genomic regions. Cell140, 678–691.

Cold Spring Harbor Laboratory, 1 BungtownRoad, Cold Spring Harbor, NY 11724, USA.E-mail: yjacob@cshl.edu, martiens@cshl.edu

DOI: 10.1016/j.cub.2010.11.052

Photoperiodism: Shall EYA CompareThee to a Summer’s Day?

Seasonal changes in day length are used by plants and animals to synchronizeannual rhythms in reproduction, physiology, and behavior to the environment.Increasing day length during spring causes sudden changes in the mammalianreproductive system once the critical photoperiod is reached. The molecularmechanism behind this switch is now quickly being elucidated.

Roelof A. Hut

The course of the seasons may notcome as a surprise to us anymore.They come and go naturally and seemto have relatively minor influences onhuman biology in modern societies,but seasonal changes in theenvironment do have profound impactin nature. Driven by changes in day

length and temperature, primaryproduction and reproduction by plantsshow strong fluctuations over thecourse of the year. Invertebrates thatdepend on external temperature fordevelopment will arrest their growthor reproduction and go into diapausein the fall. As a result, many organismshigher up in the food chainwill also facelimited resources during fall and winter.

For this reason, terrestrial organismstend to reproduce only in the springand summer, when temperature andfood conditions are more favourable.In most populations, timing ofreproduction is therefore under strongselection pressure: when reproductionstarts too early, the growing offspringface low temperatures and resourcestend to be scarce, while latereproduction leaves less time forconsecutive reproductive attemptsand little time to prepare for thefollowing winter. Accurate annualtiming is therefore an essentialcomponent of life history strategiesin organisms living in seasonalenvironments.Plants and animals have developed

accurate annual timing mechanismsthat use changing day length as the

Gonadotropins

Gonadalactivation

IMLSCG

Pineal

SCN

PVN

Retina

Photoperiod

Melatonin

Winter

Summer

Parstuberalis

Tanycytes

GnRHneurons

TSHWinter

Summer

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TH (T4)TH (T3)

DIO2

Figure 1. The photoperiod input pathway to the mammalian reproductive system.

Photoperiod is perceived by photoreceptors (melanopsin-containing ganglion cells) in theretina, which project directly to the suprachiasmatic nucleus (SCN). The SCN generates circa-dian rhythms that alternate between stimulatory and inhibitory signals to neurons in the hypo-thalamic paraventricular nucleus (PVN), which drive pineal melatonin production via autono-mous projections (via the intermediolateral column of the spinal cord (IML) and the superiorcervical ganglion (SCG)). Pineal melatonin is released in the bloodstream at night and formsthe internal mirror image of day length. It binds to the melatonin receptors in the highly vascu-larised pars tuberalis (PT), where it induces TSH production under long photoperiod. The highlevels of TSH cause the hypothalamic tanycytes in the third ventricle wall to produce the activeform (T3) of thyroid hormone from the inactive form (T4) through increased expression of theenzyme DIO2. The dashed arrow indicates a rather unknown part of the pathway (see text)which is either a direct or indirect effect of T3, and possibly other hypothalamic signals, onGnRH-producing neurons, which subsequently drive gonadotropin production in the anteriorpituitary gland, leading to gonadal activation in spring when day length increases beyonda specific critical photoperiod. Arrow connectors indicate stimulatory connections; flatconnectors indicate inhibitory connections.

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external cue to synchroniseendogenous circannual timing, whichis especially apparent in long-livedspecies. In recent years, scientistshave made impressive progressto unravel the molecular andphysiological mechanisms behindthese phenomena. So far, the parstuberalis (PT) of the pituitary appearsto be critical in photoperiod-inducedswitching between reproductivestates, but the precise molecularmechanism behind this switch wasunclear. This major gap in ourunderstanding now seems to beclosed by two publications in a recentissue of Current Biology that describethe molecular mechanism ofphotoperiodic control of mammalianreproductive timing. In one study, Soaysheep were used as the primary modelspecies [1], and in the othera melatonin-proficient laboratory strainof house mice [2]. Both studies haveyielded remarkably similar results indescribing the photoperiod-dependenttranscription factor mechanism thatflicks the reproductive switch at theright time.

This reproductive switch centres onthe action of the hormone melatoninon the PT, a highly vascularised partof the pituitary stalk that is intimatelyapposed to the median eminence atthe base of the hypothalamus.Melatonin production by the pinealgland is under the control of thecircadian system and can also bedirectly suppressed by light (Figure 1).The result is that the release ofmelatonin into the blood is confinedto the night, and when day lengthincreases during summer, the durationof the melatonin signal is shortened.Thus, melatonin is the internal mirrorrepresentation of day length.

Melatonin forms a critical componentof the photoperiodic response and ithas a profound action in the PT. The PTis packed with melatonin receptors [3]and responds under long photoperiodby increasing expression of the genecoding for thyroid stimulating hormonesubunit-b (Tshb; Figure 1). TSHb forms,together with glycoprotein subunit-a (GSUa), thyroid stimulating hormone(TSH, or thyrotropin), which in turnregulates thyroid hormone deiodinasetype-2 (Dio2) expression in the adjacentmedial basal hypothalamus. Here, Dio2is expressed in a specializedpopulation of ependymal cells liningthe cerebral ventricles known astanycytes. The DIO2 enzyme

transforms the inactive form of thyroidhormone (T4) to its active form (T3), andhence it appears that tanycytes controllocal T3 actions in the basalhypothalamus. T3 was shown toultimately influence the activity ofgonadotropin releasing hormone(GnRH)-producing neurons, which arethe critical element that drives gonadalactivation. Direct evidence that thisregulation of T3 availability is crucial forseasonal control of reproductioncomes from earlier studies in mammals[4,5], as well as in birds [6]. How T3impacts on the reproductive system isstill unclear (see dashed arrow inFigure 1), but direct or indirect actionson the GnRH neurons, which driveanterior pituitary secretion of thegonadotropins (follicle stimulatinghormone and luteinizing hormone),

must be crucial (Figure 1). Here itdeserves attention that not allcircannual rhythms depend on T3 fortheir synchronisation. The circannualprolactin rhythm in sheep drivingmoult depends on the action ofmelatonin in the PT [7] but seemsindependent of thyroid hormone [5].Until recently, it was thought that

TSH production was specific for thepituitary (pars distalis) to drive THproduction in the thyroid gland.The discovery of hypothalamicparacrine TSH and TH (T3) productionas a critical element of photoperiodicregulation has been a major stepforward, and the molecularcomponents are now being resolved.The two papers by Dardente et al. [1]

and Masumoto et al. [2] focus on themolecular mechanism of the long

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photoperiod (LP) inductionofTshb in thePT in sheep and in mice, respectively.Although their initial methodologicalstarting points differ considerably, theirconclusions are remarkably similar.Both studies find that Tshb is inducedvia the synergistic action of thetranscription factors EYA3, SIX1, andTEF (and to a lesser extent HLF). Bothstudies also indicate interesting regionsof the Tshb promoter that are eitherstrongly conserved or highlypolymorphic across a range of species.One of these regions is the D-element(or D-box) in the Tshb promoter thatbinds TEF and HLF. This D-elementwas found to be essential in tuningTEF-driven Tshb expression whenvarious forms of the D-element,occurring in different species, werescreened for their efficiency to drivetranscription [1,2]. This suggests thatmuch of the transcription factor bindingefficiency has been shaped by species-specific selection pressures.

The finding that TEF is stronglyinvolved in this PT-basedphotoperiodic mechanism isinteresting since TEF was found to playa role in the circadian timing system [8].Since the early days of circadianbiology, scientists have hypothesisedon the role for circadian clocks inphotoperiodism, leading to basicallythree models: the hour glass model,the external coincidence timing model(or ‘Bunning’s hypothesis’) [9], and theinternal coincidence timing model(or ‘Pittendrigh’s hypothesis’) [10].In short, these hypotheses formulatethat photoperiodism involves either norole for circadian clocks, but rathersome accumulating process thatincreases as a function of day length(hour glass); an interaction betweena circadian clock that drivesa photosensitive phase and light(external coincidence); or an interactionbetween two circadian oscillators, onefollowing dawn and the other followingdusk (internal coincidence; see [11] forreview). The mammalian photoperiodicpathway (Figure 1) involves severalplaces in which a circadian mechanismmay play a role, but it has been bestdescribed for the suprachiasmaticnucleus (SCN) and the PT [12]. In theSCN there is molecular [13–16] andelectrophysiological evidence [17,18]that different single-cell oscillatorsare simultaneously entrained eitherto dawn or to dusk, consistent withPittendrigh’s internal coincidencetiming model. In the PT, however,

the studies of Dardente et al. [1]and Masumoto et al. [2] suggesta mechanism that is similar toBunning’s external coincidence timingmechanism (see Figure 4 in [1]), inwhich Eya3 expression is always timedw12 h after dark onset and setsa ‘photosensitive phase’. Takentogether, it seems that the circadiansystem uses both internal and externalcoincidence timing mechanismssimultaneously to stabilize thephotoperiodic response mechanismin mammals. The balance betweenthe twomechanismsmay vary betweenspecies, enabling functional tuning tovariation in the light environment towhich different species are exposed.

So far, the story on the photoperiodicsystem seems to be wonderfullyconverging to a conserved systemin vertebrates involving hypothalamicthyroid hormone (T3) availability, but theDevil seems to be in the details again. Infact, the combined findings in theDardente et al. [1] and Masumoto et al.[2] studies raise two interesting issues.Firstly,Masumoto et al. [2] describe thatthe photoperiodic induction systemseems to be preserved in housemice allthe way down to T3 production(Figure 1), yet the reproductive systemof house mice (even the melatonin-proficient ones) is normally notresponsive to photoperiod. Moreover,Dardenteetal. [1] come to thesurprisingfinding that themouse formof theD-boxis by far the most efficient one to driveTEF-dependent gene expression ofTshb. Both findings seem unexpectedbecause mice are usually classified ashaving an ‘opportunistic’ reproductionstrategy: they seem to reproducewhenever enough food is available.On the other hand, sheep were foundto have about 50% lower D-boxefficiency, but sheep have strongphotoperiodic induction of theirreproductive system and establishedcircannual rhythms [7]. This opens thepossibility that house mice are in facta photoperiodic species, but only whenother factors like food or temperatureare considered to play an additionalinteracting role. It seems fair to saythat the mechanisms behind suchinteractions deserve more attentionin future research.

Secondly, both studies indicate thatmice and sheep share essentially thesame photoperiodic inductionmechanism upstream of the GnRHneurons (Figure 1). But, small mammalshave short gestation times (weeks) and

are so called ‘long day breeders’; i.e.they mate in spring time when days arelengthening. Larger mammals like deerand sheep have much longer gestationtimes (months) and are so called ‘shortday breeders’; i.e. they mate in autumnwhen days are shortening. Theoffspring of both ‘long day breeders’and ‘short day breeders’ will be born inspring time due to the difference ingestation time. If long and short daybreeders share a similar photoperiodicinduction mechanism for T3, then thesurprising conclusion could be that thedifference between long and short daybreeders lies in the impact of T3 onGnRH neurosecretory activity. So far, itis unknown how this might occur, butone possibility is that neuropeptidergicpathways controlling GnRH neuronalactivity differ in their sensitivity to T3.In particular, the RF-amide signalsKisspeptin and gonadotrophininhibitory hormone (GnIH) seem to becentral to this process, possiblyexerting mutually antagonistic actionson GnRH activity [19]. Nonetheless, theprecise mechanism that distinguisheslong and short day breeders remains tobe elucidated.With the discovery of more and more

molecular bits of the photoperiodictiming mechanism puzzle, we headtowards ever more exciting times.It seems to me that in the not toodistant future we can take themolecular genetics of seasonal timingback to the field and explore preciselyhow selection pressures onreproductive timing act in nature.Evolutionary biologists have beentelling us for decades how importantsuch selective pressures are for ourunderstanding of population dynamics,life history traits, maximisation offitness, and last but not least, nature’sadaptation to climate change [20].

References1. Dardente, H., Wyse, C., Birnie, M., Dupre, S.,

Loudon, A., Lincoln, G., and Hazlerigg, D.(2010). A molecular switch for photoperiodresponsiveness in mammals. Curr. Biol. 20,2193–2198.

2. Masumoto, K., Ukai-Tadenuma, M.,Kasukawa, T., Nagano, M., Uno, K.D.,Tsujino, K., Horikawa, K., Shigeyoshi, Y., andUeda, H.R. (2010). Acute induction of Eya3 bylate-night light stimulation triggers TSHßexpression in photoperiodism. Curr. Biol. 20,2199–2206.

3. Morgan, P.J., Barrett, P., Howell, H.E., andHelliwell, R. (1994). Melatonin receptors:localization, molecular pharmacology andphysiological significance. Neurochem. Int. 24,101–146.

4. Anderson, G.M., Hardy, S.L., Valent, M.,Billings, H.J., Connors, J.M., andGoodman, R.L. (2003). Evidence that thyroid

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hormones act in the ventromedial preoptic areaand the premammillary region of the brain toallow the termination of the breeding season inthe ewe. Endocrinology 144, 2892–2901.

5. Barrett, P., Ebling, F.J., Schuhler, S., Wilson, D.,Ross, A.W., Warner, A., Jethwa, P., Boelen, A.,Visser, T.J., Ozanne, D.M., et al. (2007).Hypothalamic thyroid hormone catabolism actsas a gatekeeper for the seasonal control ofbody weight and reproduction. Endocrinology148, 3608–3617.

6. Yoshimura, T., Yasuo, S., Watanabe, M., IIgo, M.,Yamamura, T., Hirunagi, K., and Ebihara, S.(2003). Light-induced hormone conversion of T4to T3 regulates photoperiodic response ofgonads in birds. Nature 426, 178–181.

7. Lincoln, G.A., Clarke, I.J., Hut, R.A., andHazlerigg, D.G. (2006). Characterizinga mammalian circannual pacemaker. Science314, 1941–1944.

8. Fonjallaz, P., Ossipow, V., Wanner, G., andSchibler, U. (1996). The two PAR leucine zipperproteins, TEF and DBP, display similarcircadian and tissue-specific expression, buthave different target promoter preferences.EMBO J. 15, 351–362.

9. Bunning, E. (1936). Die endogeneTagesrhythmik als Grundlage derphotoperiodischen Reaktion. Ber. dtsch. bot.Ges. 54, 590–607.

10. Pittendrigh, C.S., and Bruce, V.G. (1959). Dailyrhythms as coupled oscillator systems and

their relation to thermoperiodism andphotoperiodism. In Photoperiodism andRelated Phenomena in Plants and Animals,Withrow., ed. (Washington: A.A.A.S),pp. 475–505.

11. Foster, R.G., and Kreitzman, L. (2009). Seasonsof Life (London: Profile Books Ltd).

12. Wagner, G.C., Johnston, J.D., Clarke, I.J.,Lincoln, G.A., and Hazlerigg, D.G. (2008).Redefining the limits of day lengthresponsiveness in a seasonal mammal.Endocrinology 149, 32–39.

13. Hazlerigg, D.G., Ebling, F.J.P., andJohnston, J.D. (2005). Photoperiod differentiallyregulates gene expression rhythms in therostral and caudal SCN. Curr. Biol. 15,R449–R450.

14. Naito, E., Watanabe, T., Tei, H., Yoshimura, T.,and Ebihara, S. (2008). Reorganization of thesuprachiasmatic nucleus coding for day length.J. Biol. Rhythms 23, 140–149.

15. Inagaki, N., Honma, S., Ono, D., Tanahashi, Y.,and Honma, K. (2007). Separate oscillating cellgroups in mouse suprachiasmatic nucleuscouple photoperiodically to the onset and endof daily activity. Proc. Natl. Acad. Sci. USA 104,7664–7669.

16. Sosniyenko, S., Hut, R.A., Daan, S., andSumova, A. (2009). Influence of photoperiodduration and light-dark transitions onentrainment of Per1 and Per2 gene and proteinexpression in subdivisions of the mouse

suprachiasmatic nucleus. Eur. J. Neurosci. 30,1802–1814.

17. Jagota, A., De la Iglesia, H.O., andSchwartz, W.J. (2000). Morning and eveningcircadian oscillations in thesuprachiasmatic nucleus in vitro. Nat. Neurosci.3, 372–376.

18. VanderLeest, H.T., Houben, T., Michel, S.,DeBoer, T., Albus, H., Vansteensel, M.J.,Block, G.D., and Meijer, J.H. (2007).Seasonal encoding by the circadianpacemaker of the SCN. Curr. Biol. 17,468–473.

19. Kriegsfeld, L.J. (2006). Driving reproduction:RFamide peptides behind the wheel. Horm.Behav. 50, 655–666.

20. Bradshaw, W.E., and Holzapfel, C.M. (2010).Light, time, and the physiology of bioticresponse to rapid climate change in animals.Annu. Rev. Physiol. 72, 147–166.

Chronobiology Unit, University of Groningen,Life Science building, Nijenborgh 7, 9747 AGGroningen, The Netherlands.E-mail: r.a.hut@rug.nl

DOI: 10.1016/j.cub.2010.11.060

Photoreceptors: UnconventionalWays of Seeing

Animals perceive light typically by photoreceptor neurons assembled in eyes,but some also use non-eye photosensory neurons. Multidendritic neuronsin the body wall of Drosophila larvae have now been shown to use anunconventional phototransduction mechanism to sense light.

Naryttza N. Diazand Simon G. Sprecher*

For animals, visual information is vitalfor detecting potential mates, food,predators or prey. Light is primarilysensed by image-formingphotoreceptors in eyes or eye-likestructures. Photoreceptor neuronsdetect photons and generateelectrical responses, through aprocesscalled ‘phototransduction’. However,eyes are not the only organs perceivinglight. Unconventional types ofnon-image-forming light perceptionare crucial for regulating physiologicalfunctions such as circadian rhythms,pupillary reflex or acute suppressionof locomotor behaviour in rodents[1–3]. Such non-image-formingphotoreceptors have been known toexist since the 1930s in invertebratespecies such as the marine gastropodsAplysia and Onchidium [4]. Morerecently, similar photoreceptors, theso-called ‘intrinsically photosensitive

retinal ganglion cells’ (ipRGCs) havealso been described in mammals [5,6].Perhaps more surprising was thediscovery of non-image-formingphotoreceptors in the eyelessnematode Caenorhabditis elegans,which has no morphologicallydistinguishable photoreceptors andlacks genes encoding opsins — thelight-sensitive G-protein coupledreceptors (GPCRs) used in canonicalphototransduction pathways ofanimal photoreceptors [7]. Now, ina recent paper, Xiang and colleagues[8] show that the Drosophilamelanogaster larval body wallpossesses non-image-formingphotoreceptors. In C. elegans as wellas in Drosophila, non-image-formingphotoreceptors seem to play a centralrole in light-avoidance behaviour.Even more surprising is the findingthat neither of these non-image-forming phototransduction pathwaysinvolves an opsin-related light-sensingprotein.

Animal photoreceptor cells come intwo principal types characterised bydistinct specialized structures thatharbour the light-sensing proteins.In ciliary photoreceptors, thelight-sensing proteins are housed ina folded ciliary membrane, while in therhabdomeric type they sit in a foldedapical cell membrane forminga rhabdom. While both photoreceptortypes may coexist in the sameorganism, ciliary photoreceptors aretypically found in vertebrates andrhabdomeric ones in invertebrates(Figure 1A,B) [9]. The canonicalphototransduction pathway in theciliary photoreceptors of vertebratesinvolves the ciliary-opsin (c-Rh). Lightbrings c-Rh to an excited state, inwhich it activates the G-protein alphasubunit (Gta), thereby stimulatinga phosphodiesterase (PDE) thathydrolyzes cyclic GMP (cGMP) toGMP. Consequently, free cGMPdecreases, causing the closing of thecyclic-nucleotide-gated (CNG) ionchannels that are open in darkness.As a final response, the cellhyperpolarizes, thus reducing orarresting the release of theneurotransmitter glutamate [9].In invertebrates, another canonicalpathway operates, established mainlybased on theDrosophila photoreceptoras a model. It involves the rhabdomericphotoprotein r-opsin (r-Rh). Absorption