The study of zebra fish shows how retinal cells keep the spacing necessary for optimal vision

In vertebrate retinas, specialized photoreceptors responsible for color vision (conical cells) are organized in patterns known as “mosaic conical”. Researchers from the Okinawa Institute of Sciences and Technology (IOIST) have discovered that a protein called DSCACM acts as an “self-evoked executor” for color detection cells in the retinas of zebra fish, ensuring that they maintain perfect spacing for optimal vision.

Their results were published In Nature communications.

Vertebrate retinas contain photoreceptor cells that convert light into neural signals. These photoreceptors are available in two main types: stems, which operate in low light; and cones, which operate in bright light and provide Vision of colors. The cones themselves are subdivided into different types depending on the specific light wavelengths they detect. In zebra fish, there are four types: the cells of the red, green, blue and UV cone.

The cone mosaic refers to the highly organized spatial arrangement of these different types of cone through the surface of the retina. Rather than being distributed at random, coastal cells Of the same type, keep distances specific from each other and form recognizable models with other types of cone. This creates a mosaic appearance when the retina is seen from the surface.

In zebra fish, the four types of cones are assembled to form a pattern of regular network -shaped cone mosaic. This model of mosaic with complex cone in Fish species was reported in this last 19th century. However, the molecules which directly regulate the formation of the conical mosaic model had not been identified between the vertebrate species.

Creation of defective mutants of the zebra fish cone

DSCAM (Down syndrome adhesion molecule of cells) is a protein that helps nerve cells connect properly during development. It was first found in humans on chromosome 21, which is linked to Down syndrome.

DSCAM proteins exist in many animals and help the nerve cells to form neural circuits without seizing themselves. The zebra fish has three versions of this protein: DSCAMA, DSCACM and DSCAML1. Only DSCACM is found in light detection cells of the eye development of zebra fish.

“Because the DSCAM regulates a self-evidence mechanism in the development of the nervous system, we have genetically modified the zebra fish for not having functional DSCACM protein to test our hypothesis that this protein is involved in the formation of conical,” explained Dr Dongpeng Hu, former PH.D. Student in the unit of Development Neurobiology of the IOIST and the first author.

“We found that the cone mosaic motif, in particular the arrangement of the red cone, is disturbed in the DSCACM mutants of Zebra fish.”

Recognition of the same cells shapes vision

At the start of the differentiation of photoreceptors in zebra fish, cone photoreceptors The thin projections called the Filopods of their apical regions were reported to prolong the thin projections; However, their physiological role in the differentiation of photoreceptors was unknown.

To clarify the role of DSCACM in the formation of the cone mosaic, the researchers used fluorescent marking techniques to visualize where DSCACM proteins are located in cells. Surprisingly, DSCACM proteins are located in the apical regions, including the spikes of the Filopodia type of conical photoreceptors.

The researchers examined the behaviors of the red cone filopods. Thanks to accelerated imaging, they discovered that the red cones extend these filopods with neighboring red cones, briefly contact, then retract in wild zebra fish. On the other hand, such a retraction dependent on the contact of the red cone filopods was not observed in the neighboring non -red cones.

This dynamic process gradually establishes an appropriate spacing between the red cones of the same type. In DSCACM mutants, however, the red cone filopods failed to retract properly after contact with the same type of red cone and have remained attached or even invade the apical surface of the neighboring red cones. This leads to an abnormal red cone regrouping and disturbed mosaic models.

Consequently, the apical filopod of the cones works like antennas to probe their environment and feel if the neighboring cones are of the same type or not. When the filopods of a red cone come into contact with another red cone, the DSCACM proteins interact, triggering a repulsive response which causes the withdrawal of the filopod. This self-assessment mechanism ensures that the red cones maintain an appropriate spacing of each other.

In addition, this self-assessment mechanism is specific to interactions between cones of the same type: red cones recognize and respond to other red cones, and the same for blue cones with other blue cones.

Interestingly, scientists have found that the DSCACM specifically regulates the spacing of the red cones, while the similar spacing mechanism between the blue cones seems to be independent of the DSCACM. Consequently, the DSCACM works as a sensor to recognize the same type of red cone during the formation of mosaic of the cone in zebra fish.

“Our IT analysis and our modeling have confirmed that this recognition and repulsion mechanism for the same types of cells could explain the models of conical mosaic observed. This represents the first identification of a molecular mechanism directly regulating the formation of conical mosaic in all species, opening potential ways to understand similar processes in other vertebrate medals”

The discovery of the role of DSCAMB in zebra fish The formation of conical mosaic has important implications for vision research. He shows the molecular base For the specific spacing of crucial photoreceptors for an optimal vision and creates opportunities to study similar mechanisms in human retinal disorders.

This knowledge could potentially advance diagnostic approaches, treatment options and retinal regeneration strategies.