Abstract
Migratory animals can detect and use the Earth’s magnetic field for orientation and navigation, sometimes over distances spanning thousands of kilometers. How they do so remains, however, one of the greatest mysteries in all sensory biology. Here, the author reviews the progress made to understand the molecular bases of the animal magnetic sense focusing on insect species, the only species in which genetic studies have so far been possible. The central hypothesis in the field posits that magnetically sensitive radical pairs formed by photoexcitation of cryptochrome proteins are key to animal magnetoreception. The author provides an overview of our current state of knowledge for the involvement of insect light-sensitive type I and light-insensitive type II cryptochromes in this enigmatic sense, and highlights some of the unanswered questions to gain a comprehensive understanding of magnetoreception at the organismal level.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Magnetoreception, the ability of an organism to sense and use the Earth’s magnetic field to accomplish a variety of navigational tasks to locate shelter, food sources or breeding grounds, is widespread in nature (Mouritsen 2018; Putman 2022). We do know that insects, birds, sea turtles, fishes, and amphibians rely on magnetic compass information to point them in the right direction (Wiltschko and Wiltschko 1972, 2005; Lohmann and Lohmann 1993; Bottesch et al. 2016; Phillips and Borland 1994; Guerra et al. 2014; Dreyer et al. 2018). Despite its fundamental role for both short- and long-range navigation, what we do not know is exactly how magnetoreception works, making the magnetic sense the least understood senses in all biology (Nordmann et al. 2017). In this short review, the author aims to integrate recent research outcomes and progress made to understand this enigmatic sense at a mechanistic level from molecules to behavior, with a focus on insects.
With a rich repertoire of navigational behaviors, insects have emerged as promising experimental models to study magnetoreception. Some of the most remarkable examples of animals using the geomagnetic field for navigation are long-distance migratory species. Similar to birds and sea turtles which utilize the geomagnetic field as a compass cue for orientation (Wiltschko and Wiltschko 2005; Lohmann et al. 2004), migratory insects like the diurnal American monarch butterfly (Danaus plexippus) and the nocturnal Australian bogong moth (Agrotis infusa) appear to rely, at least in part, on magnetic cues for orientation during their migratory journeys (Dreyer et al. 2018; Guerra et al. 2014). Other species of navigators such as desert ants can also use the geomagnetic field for shorter range navigational tasks. Cataglyphis desert ants use the geomagnetic field for path integration, a navigation strategy that integrates information of the direction and distance traveled relative to its starting point, allowing them to align their gaze directions toward the nest entrance during their initial learning walks (Fleischmann et al. 2018, 2020). Many more species, including bees, cockroaches, firebugs, and fruit flies, have been shown to be magnetosensitive (Vale and Acosta-Avalos 2021; Netusil et al. 2021; Gould et al. 1978; Bazalova et al. 2016; Fedele et al. 2014b; Gegear et al. 2008; Oh et al. 2020), although the ecological significance of a magnetic sense in these species remains often unclear.
Because of its ability to respond to magnetic fields and its genetic tractability, the fruit fly Drosophila melanogaster has been used as a genetic model to provide the first in vivo molecular insights into magnetoreception. The lack of clear ecological significance for a magnetic sense in this species has, however, led to questioning whether findings in D. melanogaster could apply broadly in other species, including migratory birds and insects. The advent of the CRISPR–Cas9 genome editing system has started and will continue to unlock the potential for similar genetic approaches in other non-conventional model insects, including migratory ones (Wan et al. 2021). Comparative approaches should ultimately help unravel the molecular and cellular bases of the magnetic sense and their evolution across the animal kingdom.
The Earth’s magnetic field and its detection
Before diving into recent molecular advances in the field, what are the magnetic field cues animals can sense and how these signals could in theory be transduced for navigation behavior? The geomagnetic field, distributed throughout the surface of the globe, can be roughly represented by a field generated by a magnetic dipole that is tilted at an angle of about 11° with respect to the Earth’s rotational axis. It originates from the Southern hemisphere, re-enters the Earth in the Northern hemisphere, and varies in three parameters defined in biological terms as intensity, inclination, and declination (Fig. 1). The geomagnetic field intensity varies from 25 μT at the magnetic equator to 65 μT at each magnetic pole (Fig. 1A). The inclination of the field, which is the angle difference between the magnetic lines and the Earth’s surface, is 0° at the magnetic equator when the lines are parallel to the Earth’s surface and gradually changes to reach + 90° or – 90° at the magnetic Northern and Southern poles, respectively (Fig. 1A, B). Finally, the difference between true geographic north and magnetic north, called magnetic declination, varies with geographic location on the Earth's surface. As magnetic North travels, the declination angle changes by units of degrees slowly over decades. Thus, in theory, intensity, inclination, and declination of the Earth’s magnetic field provide a reference system for animals to navigate. By providing information on latitudinal position, the inclination of the geomagnetic field can be used as a navigation system for determining the direction of travel relative to the goal. When combined with the field intensity, inclination can also provide unique magnetic characteristics associated with a given location on Earth’s surface, helping animals to determine their location (i.e., map position) relative to their destination (Lohmann et al. 2004). Because of its singularity at any location and its usefulness as a cue to discriminate East–West, declination could also contribute to an animal’s map sense (Akesson et al. 2005; Chernetsov et al. 2017). Unlike birds, sea turtles, fishes, amphibians, and crustaceans in which the use of both a magnetic compass and a magnetic map has been established (for review, (Mouritsen 2018)), long-distance migratory insects have so far only been shown to use magnetic compass cues (Dreyer et al. 2018; Guerra et al. 2014).
How land animals sense the Earth’s magnetic field parameters remains far from being fully understood, but three main models have been proposed: (i) an electromagnetic induction-based model in which movement of an animal through the Earth’s magnetic field would induce a current in the inner ear (Jungerman and Rosenblum 1980; Nimpf et al. 2019); (ii) a magnetic particle-based model whereby intracellular chains of magnetite (Fe3O4) crystals would detect field intensity and function as compass needles (Uebe and Schuler 2016; Bazylinski and Frankel 2004); and (iii) a radical-pair-based model relying on the spin chemistry of radical-pair reactions initiated by light in specialized photoreceptors (Hore and Mouritsen 2016; Ritz et al. 2000; Schulten et al. 1978).
Despite being found in many organisms, including bees and ants (de Oliveira et al. 2010; Schiff 1991), magnetite has yet to be demonstrated as a magnetosensory molecule capable of regulating behavior. Similarly, evidence for electromagnetic induction is lacking in insects. More attention has been paid to the radical-pair hypothesis. The theoretical framework underlying the radical-pair mechanism posits that a light-induced electron transfer reaction generates a radical pair that can exist in singlet (antiparallel) or triplet (parallel) spin states. The Earth’s magnetic field affects the singlet–triplet interconversion in an orientation-dependent manner relative to the sensor molecule, leading to a change in the singlet–triplet yield. This in turn triggers a signaling cascade in the relevant cells, leading to a physiological and behavioral response (Hore and Mouritsen 2016; Rodgers and Hore 2009). Magnetic field effects on radical-pair reactions have been established by numerous in vitro studies (reviewed in Hore and Mouritsen 2016), albeit with field of several orders of magnitude stronger than the one on Earth’s. The proof that the photochemistry of a radical-pair mechanism is sensitive to Earth-strength magnetic fields and can function as an inclination compass has, however, been provided using a synthetic carotenoid–porphyrin–fullerene model compound (Maeda et al. 2008; Kerpal et al. 2019), further supporting the idea that a radical-pair mechanism for magnetoreception is plausible. Although not formally demonstrated in vivo, an ever-increasing amount of evidence supports this hypothesis.
Cryptochrome: a key player in insect magnetoreception
The light dependency of magnetosensitivity in many species has led the field to postulate that a photoreceptive molecule would be the candidate light-dependent magnetic detector (Ritz et al. 2000). Light-activable opsins, G protein-coupled receptors well known to function in vision, are activated when the bound chromophore retinal undergoes isomerization upon the absorption of a photon of light causing a conformational change that triggers a phototransduction cascade (Terakita 2005). Although this appeared to happen without the production of a radical pair, a recent study using quantum chemical calculations showed evidence that ultraviolet (UV) opsins can generate triplet states in a retinal chromophore (Filiba et al. 2022), rendering them potentially sensitive to the magnetic field. The other photoreceptive molecule proposed to form magnetically sensitive radical pairs of electrons is cryptochrome (CRY) flavoproteins, following photoexcitation of their flavin adenine dinucleotide (FAD) co-factor (Maeda et al. 2012). Magnetically sensitive radical pair products would be generated when the fully oxidized FAD chromophore is photoreduced via a sequence of electron transfers along a chain of tryptophan residues within the CRY polypeptide (Rodgers and Hore 2009; Wong et al. 2021; Ritz et al. 2000).
Animal CRYs, which are best known for their role in circadian function, can be classified into three categories, Drosophila-like type 1 CRYs, mammalian-like type 2 CRYs and bird-like type 4 CRYs. Drosophila-like type 1 CRYs (CRY1s) are UV-A/blue-light photoreceptors responsible for the synchronization of the circadian clock to the daily light:dark cycle (Emery et al. 2000; Zhu et al. 2005). Mammalian-like type 2 CRYs (CRY2s) do not appear to be light sensitive and function as transcriptional repressors of the heterodimeric CLOCK:BMAL1 transcription factor that drives the circadian transcriptional feedback loop (Merlin et al. 2013; Michael et al. 2017; Zhu et al. 2005). Bird-like type 4 CRYs are also light sensitive, but unlike type 1 CRYs, do not have any clock function (Zoltowski et al. 2019). In insects, the core oscillator has evolved, giving rise to at least three types of clocks based on the presence/absence of CRY1s and/or CRY2s (Yuan et al. 2007). Mammalian-like type 2 CRYs are found in all insect species examined so far with the exception of flies in the brachyceran lineage, which includes D. melanogaster (Yuan et al. 2007; Zhang et al. 2017; Zhu et al. 2005). Thus, D. melanogaster expresses only the type 1 CRY, named CRY. Several insects, like mosquitoes, butterflies, and the cockroach Blattella germanica, express both CRY1 and CRY2 (Zhu et al. 2005; Bazalova et al. 2016). Others, like the honeybee Apis mellifera, the beetle Tribolium castaneum, and the cockroach Periplaneta americana only express CRY2 (Rubin et al. 2006; Zhu et al. 2005; Bazalova et al. 2016).
Driven by the availability of genetic tools and the development of behavioral assays, the fruit fly D. melanogaster has been used to provide the first in vivo demonstration that light-sensitive type 1 CRYs mediates light-dependent magnetoreception in a wavelength-dependent manner (Fedele et al. 2014a, 2014b; Gegear et al. 2008; Yoshii et al. 2009). Responses of wild-type flies to a magnetic field under full-spectrum light were abolished when wavelengths in the CRY-sensitive, UV-A/blue part of the spectrum (< 420 nm) were blocked, as well as in Cry-null mutant flies. Unexpectedly, overexpression of monarch butterfly and human CRY2s in CRY-deficient flies restored light-dependent responses to magnetic fields (Foley et al. 2011; Gegear et al. 2010; Fedele et al. 2014a). Other studies, coupling gene knockdown or reverse genetics to behavioral analyses in the cockroaches P. americana and B. germanica, as well as in the firebug Pyrrhocoris apterus, have added support to a possible role of insect CRY2 in magnetoreception (Netusil et al. 2021; Bazalova et al. 2016). Altogether, this suggests the tantalizing possibility that type 2 CRYs may undergo the necessary photochemical reactions for magnetosensitivity (Fedele et al. 2014a; Gegear et al. 2010). Because CRY2s lack the structural features to bind FAD and current evidence indicates that, at least in mammals, type 2 CRYs do not bind FAD (Kutta et al. 2017), if CRY2 function in magnetoreception, it is likely that it would do so via an unknown mechanism. However, in striking contrast to the studies mentioned above, a recent study by our group in the monarch butterfly demonstrated that, while CRY1 is necessary for response to changes in the inclination of Earth strength magnetic fields, CRY2 is dispensable (Wan et al. 2021). The contrasting findings between this study and the one in which monarch CRY2 was overexpressed in CRY-deficient flies could be the results of CRY2 overexpression and/or the use of non-physiological magnetic field intensities in the D. melanogaster study, in which responses were rescued by monarch CRY2 but only modestly (Foley et al. 2011; Gegear et al. 2010). Nevertheless, the apparent inconsistencies on the requirement of CRY2 for magnetic responses between insect species cannot be ignored. It is conceivable that insect species that have lost the light-sensitive CRY1 evolved compensatory mechanisms for CRY2 to function in magnetoreception. However, it remains unclear why two species that have both CRY1 and CRY2 such as the monarch butterfly and the cockroach B. germanica, would display different requirements of one type of CRY over the other for magnetosensing. One formal possibility is that B. germanica CRY1 may have lost its ability to function in magnetoreception and CRY2 took on this function. The divergence of the C-terminal domain of B. germanica CRY1 from those of D. melanogaster CRY and monarch butterfly CRY1 may support such a possibility (see below). Ultimately, the use of additional insect models possessing either both CRY1 and CRY2 or only CRY2 that would be amenable to genetic manipulations and presenting robust responses to magnetic fields of intensities found on Earth would help resolve this issue.
The magnetosensitive organs: eyes and antennae as prime candidates
The anatomical localization of the site of magnetoreception has also been a sought-after area of investigation. Looking for tissue-specific expression of CRY1 and CRY2 would not yield conclusive results, given that both proteins play important roles within the circadian clock and that circadian clocks operate broadly and autonomously in all peripheral tissues in insects (Glossop and Hardin 2002). Approaches used to identify the location of magnetosensitive cells within tissues have relied on either cell type/tissue-specific rescue in D. melanogaster or blocking the light input to candidate organs with black paint in other species in which tissue-specific genetic manipulations are not yet available. In D. melanogaster, three separate anatomical locations were implicated: a subset of CRY-positive clock cells in the brain known as dorsal-lateral clock neurons (LNds), the antennae, and the eyes (Fedele et al. 2014b). Importantly, specific CRY expression in any one of these cells/organs was sufficient to restore magnetosensitivity of Cry loss-of-function mutants, suggesting some level of cellular redundancy (Fedele et al. 2014b). Interestingly, in the monarch butterfly, painting the antennae or compound eyes black resulted, in each case, in a loss of their ability to respond to a reversal of magnetic inclination (Guerra et al. 2014; Wan et al. 2021), indicating that both antennae and eyes are necessary for monarch magnetosensing and that impairing magnetosensitivity in one organ cannot be compensated by the other. Using similar painting experiments, eyes were also found to be necessary for magnetoreception in the cockroach P. americana (Bazalova et al. 2016). In this species, CRY2 immunolocalization revealed an orderly pattern of cellular expression just underneath the pigmented layer of the retina, consistent with the widely accepted view that molecules that are necessary for the transduction of a magnetic stimulus into a cellular response should be oriented in an orderly fashion (Hore and Mouritsen 2016). Determining if such a CRY expression retinal pattern is conserved across insect species and in which cells CRY is expressed in the antennae will be necessary to expand our understanding of the cellular bases of the magnetic sense.
Is cryptochrome the bona fide magnetoreceptor or a downstream signaling molecule?
While evidence for the involvement of CRYs in magnetoreception is undisputable, whether CRYs serve as bona fide magnetoreceptors or signaling molecules functioning downstream of an unknown receptor remains a debated question. As previously mentioned, CRY was originally proposed as a candidate magnetoreceptor based on its ability to initiate an electron transfer cascade along a conserved chain of Trp residues when bound to its co-factor FAD (Ritz et al. 2000; Hore and Mouritsen 2016; Rodgers and Hore 2009). However, a formal test of this hypothesis in D. melanogaster cast skepticism as mutating the terminal Trp of the Trp-triad (currently known as the Trp-tetrad) in D. melanogaster CRY and monarch CRY1 did not impair the ability of transgenic flies to respond to the magnetic field (Gegear et al. 2010; Fedele et al. 2014b). Interestingly, the C-terminal (C-ter) domain of D. melanogaster CRY, which becomes exposed once CRY undergoes conformational changes triggered by FAD photoreduction (Vaidya et al. 2013), was shown to be required for magnetosensing (Fedele et al. 2014b). As this domain does not contain the canonical FAD-binding domain and the Trp chain, this suggested that it may function in the intracellular signaling of the CRY response to magnetic fields by modulating downstream protein–protein interactions (Fedele et al. 2014b).
In an unexpected twist, recent work showed that the 52 C-ter amino acids of D. melanogaster CRY are not just required, but sufficient to facilitate magnetoreception (Bradlaugh et al. 2023) (Fig. 2A). The single Trp present on this domain does not seem to bind free FAD. Remarkably, the magnetic response mediated by the CRY C-ter can be potentiated in a dose-dependent manner by providing exogenously free FAD that is capable of forming radical pairs on its own, but not by providing its precursor riboflavin that cannot form radical pairs (Bradlaugh et al. 2023). Additionally, it appears that even in absence of the CRY C-ter, high doses of free FAD alone can cause a similar effect, suggesting that FAD may act as a magnetoreceptor at high concentration (Bradlaugh et al. 2023). Together, these results support the existence of a CRY-independent radical-pair mechanism and place CRY in the signaling cascade for magnetoreception, perhaps in addition to its receptor function.
In line with the idea that the C-ter of D. melanogaster CRY plays a role in transducing the magnetic signal, the integrity of a putative PDZ-binding motif (EEEV; Fig. 2A) to which scaffold PDZ proteins bind for the assembly and cellular localization of signaling complexes was shown to be required to support a magnetic response, as a single valine to lysine mutation is sufficient to abolish it (Bradlaugh et al. 2023) (Fig. 2A). This discovery may hold the key to deploy molecular approaches for the in vivo identification of protein interactors and perhaps transmembrane proteins that transduce the radical pair signal into a neural one, ultimately leading to behavioral responses. It may also provide a framework to settle apparent controversies related to which type of CRY (CRY1 vs. CRY2) are involved in insect magnetoreception. As previously mentioned, insect species that have lost the light-sensitive CRY1 may have evolved mechanisms for CRY2 to take on the function in magnetoreception. But what about insect species that possess both CRYs but use either CRY1 or CRY2 in a species-specific way, as is the case for the monarch and the cockroach B. germanica? Perhaps the answer lies in the CRY1 C-ter region. Aligning C-ters of D. melanogaster CRY and CRY1s from the monarch and the cockroach B. germanica reveals that monarch CRY1 C-ter exhibits a high degree of conservation with that of D. melanogaster CRY, including the presence of a relatively well-conserved PDZ-binding domain (EDEV), while the most distal end of B. germanica C-ter is truncated and lacks this domain (Fig. 2B). If indeed this domain is key for CRY1 function in magnetoreception, it could explain why B. germanica is relying on CRY2, and not CRY1, for magnetic responses. Given that most of the experiments conducted by Bradlaugh et al. used non-physiological magnetic fields, validating whether the necessity and sufficiency of the CRY C-ter is conserved in species relying on CRY1 and responding to physiological magnetic fields will be important. This could be achieved in the monarch butterfly via the use of CRISPR/Cas9 for the generation of truncated mutants (Markert et al. 2016; Zhang et al. 2017) and the development of transgenesis for sufficiency tests.
Concluding remarks
Due to the lack of obvious adaptive function of magnetic susceptibility in most insects studied so far, their use for the dissection of the molecular underpinnings of magnetoreception is sometimes questioned. The power of the genetic approaches that can be undertaken in D. melanogaster and the existence of a light-sensitive CRY1 and/or light-insensitive CRY2 in many other species make insects, however, uniquely suited for furthering the neurogenetic dissection of the molecular and cellular basis of magnetosensitivity. As discussed in this minireview, there is ample evidence that both types of CRYs play a critical role in magnetosensitivity in a species-specific manner, although it remains to be seen whether they function as a receptor or a downstream signaling molecule. Another major remaining challenge will be to determine how neural signals are transduced and integrated in the brain to give rise to behavioral responses, particularly in migratory insects that use magnetic fields for long-distance orientation and navigation such as the bogong moth and the monarch butterfly. The use of electrophysiological recordings with multi-electrode arrays from brains of tethered flying insects (Beetz et al. 2022) that would be orienting to magnetic fields hold great promise to identify the neural sites of integration of magnetic information and its encoding. Ultimately, forward progress will require highly interdisciplinary approaches, and that the community remains open to unexpected findings as we continue to dig deeper into this fascinating sense.
References
Akesson S, Morin J, Muheim R, Ottosson U (2005) Dramatic orientation shift of white-crowned sparrows displaced across longitudes in the high Arctic. Curr Biol 15(17):1591–1597. https://doi.org/10.1016/j.cub.2005.07.027
Bazalova O, Kvicalova M, Valkova T, Slaby P, Bartos P, Netusil R, Tomanova K, Braeunig P, Lee HJ, Sauman I, Damulewicz M, Provaznik J, Pokorny R, Dolezel D, Vacha M (2016) Cryptochrome 2 mediates directional magnetoreception in cockroaches. Proc Natl Acad Sci U S A 113(6):1660–1665. https://doi.org/10.1073/pnas.1518622113
Bazylinski DA, Frankel RB (2004) Magnetosome formation in prokaryotes. Nat Rev Microbiol 2(3):217–230. https://doi.org/10.1038/nrmicro842
Beetz MJ, Kraus C, Franzke M, Dreyer D, Strube-Bloss MF, Rossler W, Warrant EJ, Merlin C, El Jundi B (2022) Flight-induced compass representation in the monarch butterfly heading network. Curr Biol 32(2):338-349.e335. https://doi.org/10.1016/j.cub.2021.11.009
Bottesch M, Gerlach G, Halbach M, Bally A, Kingsford MJ, Mouritsen H (2016) A magnetic compass that might help coral reef fish larvae return to their natal reef. Curr Biol 26(24):R1266–R1267. https://doi.org/10.1016/j.cub.2016.10.051
Bradlaugh AA, Fedele G, Munro AL, Hansen CN, Hares JM, Patel S, Kyriacou CP, Jones AR, Rosato E, Baines RA (2023) Essential elements of radical pair magnetosensitivity in Drosophila. Nature 615(7950):111–116. https://doi.org/10.1038/s41586-023-05735-z
Chernetsov N, Pakhomov A, Kobylkov D, Kishkinev D, Holland RA, Mouritsen H (2017) Migratory eurasian reed warblers can use magnetic declination to solve the longitude problem. Curr Biol 27(17):2647. https://doi.org/10.1016/j.cub.2017.07.024
de Oliveira JF, Wajnberg E, Esquivel DM, Weinkauf S, Winklhofer M, Hanzlik M (2010) Ant antennae: are they sites for magnetoreception? J R Soc, Interface 7(42):143–152. https://doi.org/10.1098/rsif.2009.0102
Dreyer D, Frost B, Mouritsen H, Gunther A, Green K, Whitehouse M, Johnsen S, Heinze S, Warrant E (2018) the earth’s magnetic field and visual landmarks steer migratory flight behavior in the nocturnal australian bogong moth. Curr Biol. 28(13):2160-2166.e2165. https://doi.org/10.1016/j.cub.2018.05.030
Emery P, Stanewsky R, Helfrich-Forster C, Emery-Le M, Hall JC, Rosbash M (2000) Drosophila CRY is a deep brain circadian photoreceptor. Neuron 26(2):493–504. https://doi.org/10.1016/s0896-6273(00)81181-2
Fedele G, Edwards MD, Bhutani S, Hares JM, Murbach M, Green EW, Dissel S, Hastings MH, Rosato E, Kyriacou CP (2014) Genetic analysis of circadian responses to low frequency electromagnetic fields in Drosophila melanogaster. PLoS Genet 10(12):e1004804. https://doi.org/10.1371/journal.pgen.1004804
Fedele G, Green EW, Rosato E, Kyriacou CP (2014b) An electromagnetic field disrupts negative geotaxis in Drosophila via a CRY-dependent pathway. Nat Commun 5:4391. https://doi.org/10.1038/ncomms5391
Filiba O, Borin VA, Schapiro I (2022) The involvement of triplet states in the isomerization of retinaloids. Phys Chem Chem Phys 24(42):26223–26231. https://doi.org/10.1039/d2cp03791b
Fleischmann PN, Grob R, Muller VL, Wehner R, Rossler W (2018) The geomagnetic field is a compass cue in cataglyphis ant navigation. Curr Biol 28(9):1440-1444.e1442. https://doi.org/10.1016/j.cub.2018.03.043
Fleischmann PN, Grob R, Rossler W (2020) Magnetoreception in Hymenoptera: importance for navigation. Anim Cogn 23(6):1051–1061. https://doi.org/10.1007/s10071-020-01431-x
Foley LE, Gegear RJ, Reppert SM (2011) Human cryptochrome exhibits light-dependent magnetosensitivity. Nat Commun 2:356. https://doi.org/10.1038/ncomms1364
Gegear RJ, Casselman A, Waddell S, Reppert SM (2008) Cryptochrome mediates light-dependent magnetosensitivity in Drosophila. Nature 454(7207):1014–1018. https://doi.org/10.1038/nature07183
Gegear RJ, Foley LE, Casselman A, Reppert SM (2010) Animal cryptochromes mediate magnetoreception by an unconventional photochemical mechanism. Nature 463(7282):804–807. https://doi.org/10.1038/nature08719
Glossop NR, Hardin PE (2002) Central and peripheral circadian oscillator mechanisms in flies and mammals. J Cell Sci 115(Pt 17):3369–3377. https://doi.org/10.1242/jcs.115.17.3369
Gould JL, Kirschvink JL, Deffeyes KS (1978) Bees have magnetic remanence. Science 201(4360):1026–1028. https://doi.org/10.1126/science.201.4360.1026
Guerra PA, Gegear RJ, Reppert SM (2014) A magnetic compass aids monarch butterfly migration. Nat Commun 5:4164. https://doi.org/10.1038/ncomms5164
Hore PJ, Mouritsen H (2016) The radical-pair mechanism of magnetoreception. Annu Rev Biophys 45:299–344. https://doi.org/10.1146/annurev-biophys-032116-094545
Jungerman RL, Rosenblum B (1980) Magnetic induction for the sensing of magnetic fields by animals–an analysis. J Theor Biol 87(1):25–32. https://doi.org/10.1016/0022-5193(80)90217-9
Kerpal C, Richert S, Storey JG, Pillai S, Liddell PA, Gust D, Mackenzie SR, Hore PJ, Timmel CR (2019) Chemical compass behaviour at microtesla magnetic fields strengthens the radical pair hypothesis of avian magnetoreception. Nat Commun. https://doi.org/10.1038/s41467-019-11655-2
Kutta RJ, Archipowa N, Johannissen LO, Jones AR, Scrutton NS (2017) Vertebrate cryptochromes are vestigial flavoproteins. Sci Rep 7:44906. https://doi.org/10.1038/srep44906
Lohmann KJ, Lohmann C (1993) A light-independent magnetic compass in the leatherback sea turtle. Biol Bull 185(1):149–151. https://doi.org/10.2307/1542138
Lohmann KJ, Lohmann CM, Ehrhart LM, Bagley DA, Swing T (2004) Animal behaviour: geomagnetic map used in sea-turtle navigation. Nature 428(6986):909–910. https://doi.org/10.1038/428909a
Maeda K, Henbest KB, Cintolesi F, Kuprov I, Rodgers CT, Liddell PA, Gust D, Timmel CR, Hore PJ (2008) Chemical compass model of avian magnetoreception. Nature 453(7193):387–390. https://doi.org/10.1038/nature06834
Maeda K, Robinson AJ, Henbest KB, Hogben HJ, Biskup T, Ahmad M, Schleicher E, Weber S, Timmel CR, Hore PJ (2012) Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor. P Natl Acad Sci USA 109(13):4774–4779. https://doi.org/10.1073/pnas.1118959109
Markert MJ, Zhang Y, Enuameh MS, Reppert SM, Wolfe SA, Merlin C (2016) Genomic access to monarch migration using TALEN and CRISPR/Cas9-mediated targeted mutagenesis. G3 (Bethesda) 6(4):905–915. https://doi.org/10.1534/g3.116.027029
Merlin C, Beaver LE, Taylor OR, Wolfe SA, Reppert SM (2013) Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases. Genome Res 23(1):159–168. https://doi.org/10.1101/gr.145599.112
Michael AK, Fribourgh JL, Van Gelder RN, Partch CL (2017) Animal cryptochromes: divergent roles in light perception circadian timekeeping and beyond. Photochem Photobiol 93(1):128–140. https://doi.org/10.1111/php.12677
Mouritsen H (2018) Long-distance navigation and magnetoreception in migratory animals. Nature 558(7708):50–59. https://doi.org/10.1038/s41586-018-0176-1
Netusil R, Tomanova K, Chodakova L, Chvalova D, Dolezel D, Ritz T, Vacha M (2021) Cryptochrome-dependent magnetoreception in a heteropteran insect continues even after 24 h in darkness. J Exp Biol. https://doi.org/10.1242/jeb.243000
Nimpf S, Nordmann GC, Kagerbauer D, Malkemper EP, Landler L, Papadaki-Anastasopoulou A, Ushakova L, Wenninger-Weinzierl A, Novatchkova M, Vincent P, Lendl T, Colombini M, Mason MJ, Keays DA (2019) A putative mechanism for magnetoreception by electromagnetic induction in the pigeon inner ear. Curr Biol 29(23):4052-4059.e4054. https://doi.org/10.1016/j.cub.2019.09.048
Nordmann GC, Hochstoeger T, Keays DA (2017) Magnetoreception-a sense without a receptor. PLoS Biol 15(10):e2003234. https://doi.org/10.1371/journal.pbio.2003234
Oh IT, Kwon HJ, Kim SC, Kim HJ, Lohmann KJ, Chae KS (2020) Behavioral evidence for geomagnetic imprinting and transgenerational inheritance in fruit flies. Proc Natl Acad Sci U S A 117(2):1216–1222. https://doi.org/10.1073/pnas.1914106117
Phillips J, Borland S (1994) Use of a specialized magnetoreception system for homing by the eastern red-spotted newt Notophthalmus viridescens. J Exp Biol 188(1):275–291. https://doi.org/10.1242/jeb.188.1.275
Putman NF (2022) Magnetosensation. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 208(1):1–7. https://doi.org/10.1007/s00359-021-01538-7
Ritz T, Adem S, Schulten K (2000) A Model for photoreceptor-based magnetoreception in birds. Biophys J 78(2):707–718. https://doi.org/10.1016/s0006-3495(00)76629-x
Rodgers CT, Hore PJ (2009) Chemical magnetoreception in birds: the radical pair mechanism. Proc Natl Acad Sci U S A 106(2):353–360. https://doi.org/10.1073/pnas.0711968106
Rubin EB, Shemesh Y, Cohen M, Elgavish S, Robertson HM, Bloch G (2006) Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock. Genome Res 16(11):1352–1365. https://doi.org/10.1101/gr.5094806
Schiff H (1991) Modulation of spike frequencies by varying the ambient magnetic field and magnetite candidates in bees (Apis mellifera). Comp Biochem Physiol A Comp Physiol 100(4):975–985. https://doi.org/10.1016/0300-9629(91)90325-7
Schulten K, Swenberg CE, Weller A (1978) A biomagnetic sensory mechanism based on magnetic field modulated coherent electron spin motion. Z Phys Chem 111(1):1–5. https://doi.org/10.1524/zpch.1978.111.1.001
Terakita A (2005) The opsins. Genome Biol 6(3):213. https://doi.org/10.1186/gb-2005-6-3-213
Uebe R, Schuler D (2016) Magnetosome biogenesis in magnetotactic bacteria. Nat Rev Microbiol 14(10):621–637. https://doi.org/10.1038/nrmicro.2016.99
Vaidya AT, Top D, Manahan CC, Tokuda JM, Zhang S, Pollack L, Young MW, Crane BR (2013) Flavin reduction activates Drosophila cryptochrome. Proc Natl Acad Sci U S A 110(51):20455–20460. https://doi.org/10.1073/pnas.1313336110
Vale JO, Acosta-Avalos D (2021) Magnetosensitivity in the stingless bee Tetragonisca angustula: magnetic inclination can alter the choice of the flying departure angle from the nest. Bioelectromagnetics 42(1):51–59. https://doi.org/10.1002/bem.22312
Wan G, Hayden AN, Iiams SE, Merlin C (2021) Cryptochrome 1 mediates light-dependent inclination magnetosensing in monarch butterflies. Nat Commun 12(1):771. https://doi.org/10.1038/s41467-021-21002-z
Wiltschko W, Wiltschko R (1972) Magnetic compass of European robins. Science 176(4030):62–64. https://doi.org/10.1126/science.176.4030.62
Wiltschko W, Wiltschko R (2005) Magnetic orientation and magnetoreception in birds and other animals. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 191(8):675–693. https://doi.org/10.1007/s00359-005-0627-7
Wong SY, Wei Y, Mouritsen H, Solov’yov IA, Hore PJ (2021) Cryptochrome magnetoreception: four tryptophans could be better than three. J R Soc Interface 18(184):20210601. https://doi.org/10.1098/rsif.2021.0601
Yoshii T, Ahmad M, Helfrich-Forster C (2009) Cryptochrome mediates light-dependent magnetosensitivity of Drosophila’s circadian clock. PLoS Biol 7(4):e1000086. https://doi.org/10.1371/journal.pbio.1000086
Yuan Q, Metterville D, Briscoe AD, Reppert SM (2007) Insect cryptochromes: gene duplication and loss define diverse ways to construct insect circadian clocks. Mol Biol Evol 24(4):948–955. https://doi.org/10.1093/molbev/msm011
Zhang Y, Markert MJ, Groves SC, Hardin PE, Merlin C (2017) Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity. Proc Natl Acad Sci U S A 114(36):E7516–E7525. https://doi.org/10.1073/pnas.1702014114
Zhu H, Yuan Q, Briscoe AD, Froy O, Casselman A, Reppert SM (2005) The two CRYs of the butterfly. Curr Biol 15(23):R953-954. https://doi.org/10.1016/j.cub.2005.11.030
Zoltowski BD, Chelliah Y, Wickramaratne A, Jarocha L, Karki N, Xu W, Mouritsen H, Hore PJ, Hibbs RE, Green CB, Takahashi JS (2019) Chemical and structural analysis of a photoactive vertebrate cryptochrome from pigeon. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.1907875116
Acknowledgements
The author thanks Dr. Jerome Menet for feedback on the manuscript. This work is supported by a Texas A&M Presidential Impact Fellowship to C.M.
Funding
Texas A&M University.
Author information
Authors and Affiliations
Contributions
CM wrote the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The author declares no competing interests.
Additional information
Handling Editor: Eric J. Warrant.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Merlin, C. Insect magnetoreception: a Cry for mechanistic insights. J Comp Physiol A 209, 785–792 (2023). https://doi.org/10.1007/s00359-023-01636-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00359-023-01636-8