Blind Mammal Research Articles

Gene loss and relaxed selection of plaat1 in vertebrates adapted to low-light environments.

Gene loss is an important mechanism for evolution in low-light or cave environments where visual adaptations often involve a reduction or loss of eyesight. The plaat gene family encodes phospholipases essential for the degradation of organelles in the lens of the eye. These phospholipases translocate to damaged organelle membranes, inducing them to rupture. This rupture is required for lens transparency and is essential for developing a functioning eye. Plaat3 is thought to be responsible for this role in mammals, while plaat1 is thought to be responsible in other vertebrates. We used a macroevolutionary approach and comparative genomics to examine the origin, loss, synteny and selection of plaat1 across bony fishes and tetrapods. We showed that plaat1 (probably ancestral to all bony fish + tetrapods) has been lost in squamates and is significantly degraded in lineages of low-visual-acuity and blind mammals and fishes. Our findings suggest that plaat1 is important for visual acuity across bony vertebrates, and that its loss through relaxed selection and pseudogenization may have played a role in the repeated evolution of visual systems in low-light environments. Our study sheds light on the importance of gene-loss in trait evolution and provides insights into the mechanisms underlying visual acuity in low-light environments.

Comparative Neurology of Circadian Photoreception: The Retinohypothalamic Tract (RHT) in Sighted and Naturally Blind Mammals.

The mammalian eye contains two systems for light perception: an image detecting system constituted primarily of the classical photoreceptors, rods and cones, and a non-image forming system (NIF) constituted of a small group of intrinsically photosensitive retinal ganglion cells driven by melanopsin (mRGCs). The mRGCs receive input from the outer retina and NIF mediates light entrainment of circadian rhythms, masking behavior, light induced inhibition of nocturnal melatonin secretion, pupillary reflex (PLR), and affect the sleep/wake cycle. This review focuses on the mammalian NIF and its anatomy in the eye as well as its neuronal projection to the brain. This pathway is known as the retinohypothalamic tract (RHT). The development and functions of the NIF as well as the knowledge gained from studying gene modified mice is highlighted. Furthermore, the similarities of the NIF between sighted (nocturnal and diurnal rodent species, monkeys, humans) and naturally blind mammals (blind mole rats Spalax ehrenbergi and the Iberian mole, Talpa occidentalis) are discussed in relation to a changing world where increasing exposure to artificial light at night (ALAN) is becoming a challenge for humans and animals in the modern society.

Peripheral influences during development of the CNS

The amount of cortex devoted to the representations of each sensory system varies dramatically between different species of mammal, and these differences usually reflect the species-specific emphasis and elaboration of different sensory organs. Furthermore, the central representations of sensory systems closely preserve details of their associated receptor fields. For example, the pattern of whiskers on the snout of a mouse or a rat is represented first by barrelettes in the brain stem, then by barreloids in the thalamus and finally by barrels in the cortex. And in primates a disproportionately large area of visual cortex is devoted to representing the high density of photoreceptors in the fovea.The developmental specification of cortical areas has a genetic component, although complex interactions with the periphery are also involved. Sensory organs are able to influence the development of their central representations through a variety of mechanisms, including activity-dependent synaptic plasticity and competition for neurotrophic factors. Because information about the density, topographical arrangement and diversity of receptors can be provided online by the periphery, it does not have to be duplicated in the developmental program of the brain. This gives the brain the flexibility to adapt to the body in which it finds itself, allowing variability in the periphery to be accommodated without specific changes to the brain-wiring program.The extent to which the cortex can accommodate changes in the periphery has been demonstrated by recent experiments with North American opossums [1xMassive cross-model cortical plasticity and the emergence of a new cortical area in developmentally blind mammals. Kahn, D.M. and Krubitzer, L. Proc. Natl. Acad. Sci. U. S. A. 2002; 99: 11429–11434Crossref | PubMed | Scopus (79)See all References[1]. A marsupial was chosen because the extended period of extra-uterine development allows direct access to early stages that are intra-uterine in eutherian mammals. Animals were blinded by bilateral enucleation and then allowed to develop to adulthood. Electrophyioslogical and architectonic maps of the cortex revealed marked reorganization of the sensory areas. Primary visual cortex was greatly reduced, whereas the areas of cortex responsive to either somatosensory or auditory stimuli were expanded. In addition, a new cortical field was identified in which cells were responsive to both somatosensory and auditory stimuli. The results show both the dramatic plasticity of the wiring program of the brain and the influence of the sensory periphery on cortical development. They also provide an invaluable hint as to one mechanism by which new cortical areas emerge during evolution.

Circadian genes in a blind subterranean mammal II: conservation and uniqueness of the three Period homologs in the blind subterranean mole rat, Spalax ehrenbergi superspecies.

We demonstrated that a subterranean, visually blind mammal has a functional set of three Per genes that are important components of the circadian clockwork in mammals. The mole rat superspecies Spalax ehrenbergi is a blind subterranean animal that lives its entire life underground in darkness. It has degenerated eyes, but the retina and highly hypertrophic harderian gland are involved in photoperiodic perception. All three Per genes oscillate with a periodicity of 24 h in the suprachiasmatic nuclei, eye, and harderian gland and are expressed in peripheral organs. This oscillation is maintained under constant conditions. The light inducibility of sPer1 and sPer2, which are similar in structure to those of other mammals, indicates the role of these genes in clock resetting. However, sPer3 is unique in mammals and has two truncated isoforms, and its expressional analysis leaves its function unresolved. Per's expression analysis in the harderian gland suggests an important participation of this organ in the stabilization and resetting mechanism of the central pacemaker in the suprachiasmatic nuclei and in unique adaptation to life underground.

Massive cross-modal cortical plasticity and the emergence of a new cortical area in developmentally blind mammals.

In the current investigation, the neurophysiological organization of the neocortex was examined in adult animals that were bilaterally enucleated very early in life, before the retino-geniculo-cortical pathway was established. Our results indicate that some aspects of development of cortical fields are not mediated by specific sensory inputs. However, the current study also demonstrates that peripheral innervation plays a large role in the organization of the neocortex, as cortical territories normally involved in visual processing are completely captured by the auditory and somatosensory system. Thus, a large degree of phenotypic variability in cortical organization can be accomplished solely by removing or modifying sensory inputs.

Biological clock in total darkness: the Clock/MOP3 circadian system of the blind subterranean mole rat.

Blind subterranean mole rats retain a degenerated, subcutaneous, visually blind but functionally circadian eye involved in photoperiodic perception. Here we describe the cloning, sequence, and expression of the circadian Clock and MOP3 cDNAs of the Spalax ehrenbergi superspecies in Israel. Both genes are relatively conserved, although characterized by a significant number of amino acid substitutions. The glutamine-rich area of Clock, which is assumed to function in circadian rhythmicity, is expanded in Spalax compared with that of humans and mice, and is different in amino acid composition from that of rats. We also show that MOP3 is a bona fide partner of Spalax Clock and that the Spalax Clock/MOP3 dimer is less potent than its human counterpart in driving transcription. We suggest that this reduction in transcriptional activity may be attributed to the Spalax Clock glutamine-rich domain, which is unique in its amino acid composition compared with other studied mammalian species. Understanding Clock/MOP3 function could highlight circadian mechanisms in blind mammals and their unique pattern as a result of adapting to life underground.

The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene.

The eyeless inbred mouse strain ZRDCT has long served as a spontaneous model for human anophthalmia and the evolutionary reduction of eyes that has occurred in some naturally blind mammals. ZRDCT mice have orbits but lack eyes and optic tracts and have hypothalamic abnormalities. Segregation data suggest that a small number of interacting genes are responsible, including at least one major recessive locus, ey1. Although predicted since the 1940s, these loci were never identified. We mapped ey1 to chromosome 18 using an F2 genome scan and there found a Met10-->Leu mutation in Rx/rax, a homeobox gene that is expressed in the anterior headfold, developing retina, pineal, and hypothalamus and is translated via a leaky scanning mechanism. The mutation affects a conserved AUG codon that functions as an alternative translation initiation site and consequently reduces the abundance of Rx protein. In contrast to a targeted Rx null allele, which causes anophthalmia, central nervous system defects, and neonatal death, the hypomorphic M10L allele is fully viable.

The lens protein α -B-crystallin of the blind subterranean mole-rat: high homology with sighted mammals

Blind subterranean mole rats, Spalax ehrenbergi, retain a subcutaneous, degenerated eye, which is visually non-functional but which does function in circadian entrainment. Crystallins, members of the small heat shock protein family, constitute approximately 90% of the water-soluble proteins of the transparent eye lens and are crucial for its optical properties, but they are also expressed in other tissues. In our attempt to understand the role of the eye in the blind mole-rat, we now describe the cloning, sequencing, and expression of the cDNA of α -B-Crystallin from two species of Spalax ( S. galili and S. Judaei, with diploid chromosome numbers 2 n=52 and 60, respectively). Spalax α- B-Crystallin is highly conserved. It is expressed in many tissues of Spalax, among them Spalax eye. The sequence of the cDNA of α -B-Crystallin in the eye and in the heart of Spalax is identical. Further studies are essential to clarify the role of this gene in the lens of an atrophied eye of a visually blind mammal.

P1D98 - Low dose radiation effect on proteinase-inhibitor system in agricultural plants from chernobyl zone

Blind subterranean mole rats, Spalax ehrenbergi, retain a subcutaneous, degenerated eye, which is visually non-functional but which does function in circadian entrainment. Crystallins, members of the small heat shock protein family, constitute approximately 90% of the water-soluble proteins of the transparent eye lens and are crucial for its optical properties, but they are also expressed in other tissues. In our attempt to understand the role of the eye in the blind mole-rat, we now describe the cloning, sequencing, and expression of the cDNA of α-B-Crystallin from two species of Spalax (S. galili and S. Judaei, with diploid chromosome numbers 2n=52 and 60, respectively). Spalax α- B-Crystallin is highly conserved. It is expressed in many tissues of Spalax, among them Spalax eye. The sequence of the cDNA of α-B-Crystallin in the eye and in the heart of Spalax is identical. Further studies are essential to clarify the role of this gene in the lens of an atrophied eye of a visually blind mammal.

Cross-modal neuroplasticity in the blind mole rat Spalax ehrenbergi: a WGA-HRP tracing study.

Spalax ehrenbergi is a subterranean rodent possessing extremely degenerated eyes but a distinguishable dorsal lateral geniculate nucleus (dLGN) which projects ipsilaterally to a fair sized striate cortex. 2-Deoxyglucose and electrophysiological studies have shown that these areas are vigorously activated by auditory input. We show here, using the neuroanatomical tracer WGA-HRP, that the major source of the auditory input to the visual system is the inferior colliculus that, in addition to all its typical auditory targets, also projects to the dLGN. The visual thalamo-cortical pathway thereupon processes auditory information. This is the first naturally blind mammal in which the origin of auditory compensatory projections have been traced and described.

On the functionality of the visually deprived occipital cortex in early blind persons

In early blind mammals, the deprived visual cortex undergoes anatomical and functional alterations. Its functional role was investigated in the early human blind by using patterns of cortical activation as measured by scalp-recorded event-related slow negative DC potential shifts. The blind showed higher occipital negativity than did sighted persons both during a tactile reading task and a non-reading tactile control task. Results point to a possible role for the blind's visual cortex in tactile processes.

Evolution of crystallins: expression of lens-specific proteins in the blind mammals mole (Talpa europaea) and mole rat (Spalax ehrenbergi).

The mole (Talpa europaea; Insectivora) and the mole rat (Spalax ehrenbergi; Rodentia) both have degenerated eyes as a convergent adaptation to subterranean life. The rudimentary eye lenses of these blind mammals no longer function in a visual process. The crystallin genes, which display a lens-specific expression pattern, were studied in these blind mammals and in related species with normal eyes by hybridizing their genomic DNAs with probes obtained from cDNA clones for alpha A-, alpha B-, and beta Bp-crystallins from calf and gamma 3-crystallin from the rat. For all crystallin genes examined, the hybridization signals of mole and mole rat genomic DNA were comparable, respectively, with those of shrew and of rat and mouse, normal-vision representatives of the orders Insectivora and Rodentia. The expression of the crystallins at the protein level was tested by using antiserum specific for alpha-crystallin in immunofluorescence reactions on lens sections of mole and mole rat eyes and by using antisera against the beta- and gamma-crystallins on sections of the mole eye. All antisera gave positive fluorescence reactions exclusively with lens tissue of these blind mammals, indicating that the crystallins are still normally expressed despite the fact that these lenses have had no function in a visual process in these mammals for at least many million years. These findings apparently imply that some unknown selective advantage has conserved the crystallin genes and their expression after the loss of normal function of the lenses.

Photoperiod perception in the blind mole rat (Spalax ehrenbergi, Nehring): involvement of the Harderian gland, atrophied eyes, and melatonin.

The involvement of the Harderian gland, atrophied eyes, and melatonin in the perception of photoperiodic changes has been studied in the mole rat, a fossorial blind mammal the thermoregulatory capacity of which is photoperiod-dependent. When transferred from a long photoperiod to a short one, mole rats increase their resistance to cold, a perfectly reversible phenomenon. After 2 weeks under short photoperiod the thermoregulatory capacities of animals without Harderian glands are less than those of the controls. The Harderian gland appears thus to be implicated in the detection of photoperiodic changes. After 5 weeks, however, the Harderianectomized animals had perfectly integrated the photoperiodic change, so demonstrating that other photoreceptor organs exist. The atrophied eyes, which, under these conditions, do not seem to play an important role, are involved when the animals are transferred from short photoperiod to long photoperiod. Melatonin, but not 5-methoxytryptamine, appears to be a crucial compound in such a phenomenon. These results, which demonstrate that in mammals (at least in the mole rat, as in nonmammalian vertebrates), nonocular photoreceptors exist, suggest that the mechanism by which mammals integrate photoperiodic changes is not the same when the animals are transferred from long to short photoperiod as when transferred from short photoperiod to long photoperiod.