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From mice to humans: How does Reelin affect brain evolution and structure?
Reelin is a giant secreted extracellular matrix glycoprotein encoded by the RELN gene, which mainly regulates the migration and positioning of neurons in the developing brain by controlling cell-cell interactions. In addition to its important role in early development, Reelin continues to play a role in the adult brain. It regulates synaptic plasticity by enhancing the induction and maintenance of long-term potentiation and stimulates the development of dendrites and dendritic spines in the hippocampus, while also regulating the continued migration of neuroblasts generated at sites of adult neurogenesis. Not only that, Reelin is also present in multiple parts of the body such as the liver, thyroid, adrenal glands, and plays a potential role in the cause of some neurological diseases.
Reelin expression is significantly reduced in schizophrenia and bipolar disorder, but the reason for this observation remains unclear because studies have shown that psychiatric drugs themselves can affect Reelin expression.
In mice, a complete lack of Reelin has been found to result in a type of brain dysgyria, and Reelin may play a role in a variety of conditions, including Alzheimer's disease, temporal lobe epilepsy and autism. Reelin's name comes from the abnormal gait of "reeler" mice, which were found to lack this brain protein and are homozygous for a mutation in the RELN gene.
Reelin's Discovery
Study shows that mutant mice provide insights into the molecular mechanisms of central nervous system development. Initially, scientists randomly identified some mice with movement difficulties by observing their motor behavior and gave them descriptive names such as "reeler" and "weaver". The "reeler" mouse was first described by D.S. Falconer at the University of Edinburgh in 1951, following a sudden mutation that arose in the mouse strain in 1948. Subsequent histopathological studies revealed that the cerebellum of reeler mice was significantly compacted, and the normal hierarchical structure of several brain regions was disrupted.
In the 1970s, the discovery of cell layer reversals in the mouse neocortex further attracted attention to the Reeler mutation. In 1994, a new reeler allele was obtained by insertional mutagenesis, which was the first molecular marker to locate the RELN gene to chromosome 7q22 and was subsequently cloned and identified. Japanese scientists at Kochi Medical University succeeded in generating antibodies against normal brain extracts of reeler mice. These antibodies were later called CR-50 and they reacted specifically with Cajal-Retzius neurons, whose functional role had remained unclear until this time. .
Tissue distribution and secretion of Reelin
Studies have shown that Reelin is absent from synaptic vesicles and is secreted via the constant secretory pathway and stored in Golgi secretory vesicles. The release rate of Reelin is not regulated by depolarization but is strictly dependent on its synthesis rate. During brain development, Reelin is primarily secreted by Cajal-Retzius cells and other similar cells in the cerebral cortex and hippocampus.
Reelin synthesis peaks after birth and then rapidly decreases as the baby grows, with expression becoming more diffuse. In the adult brain, Reelin is primarily expressed by GABAergic interneurons in the cortex and glutamatergic neurons in the cerebellum, and its function also changes with age.
Reelin's structure and function
Reelin's related functions have important significance in the evolution of the brain. Its structure consists of 3461 amino acids and possesses serine protease activity. Among them, 65 exons span approximately 450 kb, and two transcription start sites and two polyadenylation sites were identified in the gene structure. The main functions of Reelin include regulating cortical development and neuronal positioning, which is crucial both in the embryonic stage and in adulthood.
Evolutionary significance
The Reelin-DAB1 interaction may play a key role in the structural evolution of the cortex. Studies have shown that as the cortex becomes more complex, Reelin expression increases. Reelin is present in the telencephalon in all vertebrates studied, but its expression pattern varies greatly.
Various discoveries have shown the importance of Reelin in brain structure, especially as the human brain evolves, Reelin's role is not only in the development period, but also the cornerstone of the normal functioning of the human brain today. All of this has prompted us to further study the role of Reelin in cognitive function and mental health to explore the evolutionary significance and underlying mechanisms behind brain structure.
How big a role does Reelin play in brain evolution? Are there other undiscovered mechanisms?
