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Sea lamprey

The sea lamprey, or Petromyzon marinus, is an agnathe vertebrate – it lacks a jaw - that belongs to the superclass Cyclostomata. This species represents the most ancient group of vertebrates. They have existed for over 360 million years, and are therefore known as living fossils due to their many evolutionally conserved features.

The adult lamprey may be characterized by a toothed, funnel-like sucking mouth. They feed by boring into the flesh of other fish to suck their blood. Not all species of lamprey are parasitic. These strange animals are an important species for studying the origin and evolution of vertebrates, but also are one of the best models for researching vertebrate embryonic development and organ differentiation.

 Lampreys also have a powerful and unique immune system and many valuable genes. Based on lamprey genome research, important human disease-related genes might be discovered. In addition, lamprey genetic models of human diseases could be the key for in-depth study of the pathogenesis and treatment of diseases and development of new drugs. 



From Lampreys to other vertebrates


Lampreys existed before the time of dinosaurs, some 360 million years ago, and over these hundreds of millions of years of evolution they have since stayed almost unchanged. Lampreys are the most primitive extant vertebrates among marine organisms. They are what are called ‘living fossils’ and have therefore an important position in vertebrate evolution, which has attracted the growing attention of biologists worldwide. With the development of modern molecular techniques, lampreys have become one of the most important research models for understanding vertebrates.

The lamprey genome remains primitive compared to other higher vertebrates, and possesses abundant functional genes. Through scientific and technological progress, scientists have conducted in-depth studies on the nervous, endocrine, and immune systems of lampreys, to understand and compare them. Such research is important to understand and reveal the origin and evolution of vertebrates, and could contribute to a greater understanding of human diseases and treatments.



Developmental studies


Lamprey research began in the mid-19th century. At that time, lampreys were considered as direct ancestors of modern vertebrates. Many initial studies focused on comparing the morphological differences between adult lampreys and higher vertebrates to determine their taxonomic positions. The first lampreys to be used for those studies were all captured from the wild as larvae in 1900. Soon after, in vitro fertilization techniques and short-term feeding made the study of lamprey embryonic development possible. Embryonic development of sea lamprey was first described by George Piavis (1961). His developmental staging system are still widely used today.

The lamprey’s physical characteristics are very primitive, their tissues and organs can be compared to the initial state of vertebrate evolution and development. They do not have jaws, possess median rather than paired fins, a notochord and an incomplete skull, similar to the skulls of higher vertebrates at the early stage of embryonic development. They also have a primitive gill cage supports respiration and their digestive systems have not differentiated into stomachs. And these are only a few examples. These primitive characteristics suggest that lampreys are situated at the lowest level of vertebrate evolution. All chordates have three main features in common at a certain stage, which indicates that all chordates originated from a common ancestor. As a consequence, lampreys are not only pivotal species for studying the origin and evolution of vertebrates, but also the best model for investigating vertebrate embryonic development and organ differentiation.



The study of the brain


Understanding complex neural networks remains challenging, and the best way to start is to study vertebrates that have simple neural networks. Lampreys have relatively few nerve cells, with just one brain and one spinal cord, which makes their study relatively easy. Lampreys are widely used to study the mechanism of swimming controlled by neural networks. Lampreys also have many visible neurons, making them highly suitable for microelectrode experiments; and their neurons can survive for a long time in-vitro in separation devices, which is helpful for bionics.

The brains of lampreys possess the basic structures of the vertebrate brain, although the nervous system, neural synapses, and synaptic neurotransmitters of lampreys represent the most primitive state in vertebrates. In embryonic development, during the development process, the embryos usually repeat important stages of germline evolution. Therefore, the developing structure of the lamprey’s brain can reflect the elaborate structural changes found in higher vertebrate brains. Thus, lampreys are one of the most valuable animal models for the study of vertebrate brain development and might hold some of the keys to unlocking our understanding of human cognition and the brain map.



Looking at the hormonal system


The lamprey endocrine system is simpler than the humans’, and the endocrine organs and related molecules are more primordial. Comparing the histology and biochemistry of the primitive lamprey endocrine system with the human endocrine system that is well-differentiated, has helped better understand the evolution of the vertebrate endocrine system. Researchers have found complex patterns of endocrine mechanisms in Lampreys, regarding for example the Gonadotropin releasing hormone (GnRH), a key signalling molecule of the hypothalamic-pituitary-gonadal axis, of olfaction, gonadal development and the maturation of gametes.

 The lamprey endocrine system plays also a part in metamorphosis. As the sexual maturity in lampreys is slow, understanding how the system functions and how to control it could impact the lamprey’s use as a model organism. But this knowledge is not only beneficial for lamprey research. Finding ways to accelerate lamprey maturation could also help find therapies for human diseases caused by hormonal disorders. Moreover, research to find a way in which to promote the growth of lampreys, and studies of their endocrine systems could also one-day help contain this parasitic fish. Due to their parasitic habits, lampreys can have considerable impact on fisheries. Potentially, fish farmers could disrupt lamprey breeding, development, and migration in order to prevent damage to their fisheries.



The immune system


The origin and evolution of the adaptive immune system (AIS) remains an important field in immunological research. Jawless vertebrates are generally considered to have evolved the AIS. Clarifying the adaptive immunity of Lampreys is of great significance in revealing the origin and evolution of the AIS. Early experiments show that lampreys should have an AIS. Initially, however, T-cell receptors, B-cell receptors, and major histocompatibility complexes, which are symbolic molecules of the AIS, could not be found in lampreys.

However, recently,  an alternative set of molecules, variable lymphocyte receptors (VLRs), were found to mediate the adaptive immune responses in lampreys. These variable lymphocyte receptors (VLRs)have been crucial for research in many ways.

While currently monoclonal antibodies are widely used in research and clinical practices, these immune globulins are costly, the manufacturing techniques are complex, and their physiochemical properties are unstable. Alternatives are therefore sought.

The discovery of VLRs allow for the development of new antibody reagents and drugs. These molecules are smaller and simpler, and so are more suitable for in-vivo transport of drugs and penetration into blood vessels.

VLRs are more applicable for the development of antibody drugs than monoclonal antibodies. In addition, the relationship between lampreys and humans is not close, so VLRs have good specificity as diagnostic reagents, eliminating cross-reactivities.

Therefore, the in-depth exploration of the lamprey immune system might be contribute to defeating serious human illnesses such as cancer, AIDS, and autoimmune diseases.



Genetic studies


Over the years, studies on lampreys have been confined to ecology and physiology, while genome and proteomic research remains scarce. However, since lampreys are living fossils of ancient animals, the lamprey genome could be described as a molecular fossil of ancient genetic information. It is therefore a record of the genetic information of vertebrates hundreds of millions of years ago, and exhibits many novel genes and proteins. Today, researchers have successively constructed lamprey cDNA libraries of salivary glands, blood, liver and immune body and other tissues, and studied many genes and proteins with important physiological functions. Some of the proteins found had special function such as blood coagulation, and the researchers believe they could eventually exploit these different properties for intravenous, oral, or gene therapy drugs.

Moreover, studies on lamprey functional genes can help understand the detailed biological evolutionary process of different genes, and can also contribute to finding associated proteins or peptide drugs, which might be favourable for human disease therapy. Therefore, whether from the perspective of scientific research or application, studying the function of lamprey genes has far-reaching significance.




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