A study led by the University of Haifa found that the first cells of the primary kidney in the embryos of a river otter and a catfish appear within the somites – embryonic units from which muscles, tendons and parts of the skeleton also develop. The findings support a hypothesis put forward by a German researcher as early as 1888.
A new study led by researchers from the University of Haifa proposes to change the conventional description of the beginning of kidney development inVertebratesThe researchers found that in the embryos of two evolutionarily ancient vertebrates – The European River Pair וSmall-spotted catshark – The first cells associated with the development of the primary kidney are located within an embryonic region from which the body muscles, tendons, back skin, and parts of the skeleton also develop.
The study, published in the journal Science Advances, provides new evidence for a hypothesis that was proposed as early as 1888, but did not become the central concept in the field of developmental biology.
"This finding is not just a point correction to the evolutionary development model of the kidney," said Dr. Ram Reshef of the Department of Evolutionary and Environmental Biology at the University of Haifa, who led the study. According to him, the findings change the way researchers examine the connections between body systems in the early stages of embryo development, and raise the possibility that processes that were thought to be separate are linked to each other with deep evolutionary roots.
Three kidneys one after the other
In vertebrates, the renal system does not form all at once in its adult form. During embryonic development, several renal systems appear one after the other.
The first of these is the primary kidney, known as PronefrosIt develops in the front part of the embryo's body, in the area between the head and neck. In some fish and amphibians, the primary kidney can be a functional organ, while in mammals and birds it appears for a short time and is later replaced by more advanced renal systems.
The conventional view was that the renal systems develop from the middle mesoderm – a strip of embryonic tissue located between the area from which the muscles and skeleton develop and the area from which other internal organs form. The middle mesoderm also develops parts of the reproductive system.
The new study does not claim that the adult kidney of humans or mammals is formed directly from muscles or vertebrae. The finding concerns a much earlier stage: the location and origin of the first cells that participate in the construction of the primary kidney in ancient vertebrates.
Amphioxus, a pair and a shark
Dr. Reshef, doctoral student Pascal Schmidt and other researchers from the University of Haifa worked with colleagues from the Technion, the Sorbonne University in France and the University of Genoa in Italy.
The team examined embryos of three animals representing different stages of development.evolution Of chordates and vertebrates.
The first is Amphioxus, a small fish-like marine animal. Amphioxus is not a vertebrate, but it is evolutionarily close to vertebrates and retains some features of the ancient body structure from which it evolved.
The second species is the European river pair, a jawless fish that belongs to one of the oldest lineages of vertebrates alive today. The third is the small-spotted catshark, a jawed cartilaginous fish that represents another early branch in the vertebrate evolutionary tree.
Comparing these animals allows researchers to distinguish between mechanisms that evolved at a relatively late stage and features that may be ancient and date back to the earliest ancestors of vertebrates.
Searching for the molecular identity of cells
The researchers tracked the activity of the genes Pax2 and Lim1, which are considered early markers of cells involved in the development of the renal system. Rather than relying solely on the external shape of the tissues, they used molecular staining and imaging to identify where the genes were expressed in the embryos.
In shark and snapping turtle embryos, the first markers of the kidney appeared within the somites. Somites are embryonic segments that repeat along both sides of the embryo's body. From these, skeletal muscles, vertebrae, tendons, and part of the back skin later develop, among other things.
The region within the somite from which the kidney cells emerge is called the nephrotome. The results indicate that the nephrotome is not only adjacent to the somite, but is integrated into it in the early stages examined.
The finding also fits with what is known about Amphioxus: an ancient excretory organ in this animal also develops from a fragmented embryonic unit connected to the somites. The similarity between the species strengthens the possibility that the excretory system and the musculoskeletal system had a developmental connection early in the evolution of chordates.
The sonic hedgehog connects the kidney to the skeleton
To test whether the connection is only in the location of the cells or also in their control mechanism, the researchers examined the signal transduction pathway. Sonic the Hedgehog – "The Sonic Hedgehog."
Despite its unusual name, it is one of the most important control pathways in embryonic development. It helps determine body structure, the organization of the nervous system, and the development of the central skeleton and vertebrae.
The researchers blocked the pathway in embryos and examined how this affected early kidney markers. In the shark and the pair, the blockage also affected the development of the primary kidney. In amphioxus, however, the same dependence on the pathway was not observed.
According to the researchers, the result indicates that the mechanisms controlling kidney development have changed throughout evolution. It is possible that the link between vertebrate development and the primary kidney strengthened or changed with the emergence of vertebrates.
An idea from 1888 gets new support
The study also has a historical aspect. In 1888, German embryologist Johannes Rickert proposed that the primary kidney of sharks develops from the somite.
At that time, researchers could rely mainly on microscopic observations of tissue structure. They could not tag genes, track the molecular identity of cells, or block signaling pathways in a controlled manner.
The notion that the kidney develops from the middle mesoderm was a continuation of the mainstream explanation, while Rickert's hypothesis was marginalized. The new study does not prove that every detail of his description was correct, but it provides molecular support for the central idea that the early cells of the primary kidney in sharks are associated with somites.
Possible implications for the study of birth defects
The researchers emphasize that this is basic research, not an immediate therapeutic breakthrough. However, identifying the developmental connections between body systems may help in the future to understand birth defects in which damage to theKidneys And in the skeleton.
"If the beginning of kidney development is related to the area from which components of the skeletal system also develop, this may help in the future to better understand situations in which kidney and bone defects appear together," said Dr. Reshef.
He says this is not a promise for medical treatment, but a new way to understand how shared embryonic mechanisms may affect more than one body system.
The findings also demonstrate the contribution of evolutionary research to medicine and biology. Studying sharks, rays, and amphioxus is not just about reconstructing the appearance of an ancient animal. It allows us to identify ancient layers in the body's structural plan, some of which are still active in the embryos of modern vertebrates.
