Higher mammals, such as humans, have markedly larger brains than other mammals. Scientists from the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden recently discovered a new mechanism governing brain stem cell proliferation.
Hirn-Stammzellen (rot) in der embryonalen Großhirnrinde der Maus (Zellkerne: blau).
© MPI f. molekulare Zellbiologie und Genetik, Dresden/ D. Stenzel
It serves to boost the production of neurons during development, thus causing the enlargement of the cerebral cortex – the part of the brain that enables us humans to speak, think and dream. The surprising discovery made by the Dresden-based researchers: two components in the stem cell environment – the extracellular matrix and thyroid hormones – work together with a protein molecule found on the stem cell surface, a so-called integrin.
This likely explains why iodine deficiency in pregnant women has disastrous consequences for the unborn child, affecting its brain development adversely – without iodine, no thyroid hormones are produced. “Our study highlights this relationship and provides a potential explanation for the condition neurologists refer to as cretinism”, says Wieland Huttner, Director at the Max Planck Institute in Dresden. This neurological disorder severely impairs the mental abilities of a person.
In the course of evolution, certain mammals, notably humans, have developed larger brains than others, and therefore more advanced cognitive abilities. Mice, for example, have brains that are around a thousand times smaller than the human one. In their study, which was conducted in cooperation with the Fritz Lipmann Institute in Jena, the researchers in Dresden wanted to identify factors that determine brain development, and understand how larger brains have evolved.
A cosy bed for brain stem cells
Brain neurons are generated from stem cells called basal progenitors that are able to proliferate in humans, but not in mice. In humans, basal progenitors are surrounded by a special environment, a so-called extracellular matrix (ECM), which is produced by the progenitors themselves. Like a cosy bed, it accommodates the proliferating cells. Mice lack such ECM, which means that they generate fewer neurons and have a smaller brain.
The scientists therefore conducted tests to see whether in mice, basal progenitors start to proliferate if a comparable cell environment is simulated. The result: “We simulated an extracellular matrix for the brain stem cells using a stimulating antibody. This antibody activates an integrin on the cell surface of basal progenitors and thus stimulates their proliferation”, explains Denise Stenzel, who headed the experiments.
Because a requirement of thyroid hormones for proper brain development was previously known, the researchers blocked the production of these hormones in pregnant rats to see if their absence would inhibit basal progenitor proliferation in the embryos. Indeed, fewer progenitors and, consequently, neurons were produced, likely explaining the abnormal brain development in the absence of thyroid hormones. When the action of these hormones on the integrin was blocked, the ECM-simulating antibody alone was no longer able to induce basal progenitor proliferation.
A combination of ECM and thyroid hormones thus appears necessary for basal progenitors to proliferate and produce enough neurons for brain development. Human brain stem cells produce the suitable environment naturally. “That is probably how, in the course of evolution, we humans developed larger brains”, says Wieland Huttner, summing up the study. The research produced another important finding: “We were able to explain the role of iodine in embryonic brain development at the cellular level”, says Denise Stenzel. Iodine is essential for the production of thyroid hormones, and an iodine deficiency in pregnant women is known to have adverse effects on the brain development of the unborn child.Contact
Integrin αvβ3 and thyroid hormones promote expansion of progenitors in embryonic neocortex
Development (2014) doi: 10.1242/dev.101907
Prof. Dr. Wieland B. Huttner | Max-Planck-Institute
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy