Lifeboat Foundation

During fetal development of the mammalian brain, the cerebral cortex undergoes a marked expansion in surface area in some species, which is accommodated by folding of the tissue in species with most expanded neuron numbers and surface area. Researchers have now identified a key regulator of this crucial process.

Different regions of the mammalian brain are devoted to the performance of specific tasks. This in turn imposes particular demands on their development and structural organization. In the vertebrate forebrain, for instance, the cerebral cortex – which is responsible for cognitive functions – is remarkably expanded and extensively folded exclusively in mammalian species. The greater the degree of folding and the more furrows present, the larger is the surface area available for reception and processing of neural information. In humans, the exterior of the developing brain remains smooth until about the sixth month of gestation. Only then do superficial folds begin to appear and ultimately dominate the entire brain in humans. Conversely mice, for example, have a much smaller and smooth cerebral cortex.

“The mechanisms that control the expansion and folding of the brain during fetal development have so far been mysterious,” says Professor Magdalena Götz, a professor at the Institute of Physiology at LMU and Director of the Institute for Stem Cell Research at the Helmholtz Center Munich. Götz and her team have now pinpointed a major player involved in the molecular process that drives cortical expansion in the mouse. They were able to show that a novel nuclear protein called Trnp1 triggers the enormous increase in the numbers of nerve cells which forces the cortex to undergo a complex series of folds. Indeed, although the normal mouse brain has a smooth appearance, dynamic regulation of Trnp1 results in activating all necessary processes for the formation of a much enlarged and folded cerebral cortex.

As outlined in a study published in Developmental Cell, researchers have discovered a novel function for p27 in the control of interneuron migration in the developing cerebral cortex.

The cerebral cortex is one of the most intricate regions of the brain whose formation requires the migration and integration of two classes of neurons: the projection neurons and the interneurons. These neurons are born in different places and use distinct migration modes to reach the cortex. While several signaling pathways involving various molecules have already been associated with projection neuron migration, the molecular mechanisms that control interneurons migration remain elusive.

In this study, researchers unveiled a novel activity of p27—a protein initially described for its activity as cell cycle regulator—in dynamic remodelling of the cell skeleton. This skeleton, named cytoskeleton, underlies tangential migration of interneurons in the cerebral cortex. Juliette Godin, primary researcher states: At the molecular level, p27 acts on two cytoskeletal components, the actin and the microtubules. It promotes nucleokinesis and branching of the growth cone through regulation of actine. In addition, it promotes microtubule polymerisation in extending neurites. Both activities are required for proper tangential migration of interneurons in the cortex.

The cerebral cortex, which controls higher processes such as perception, thought and cognition, is the most complex structure in the mammalian central nervous system. Although much is known about the intricate structure of this brain region, the processes governing its formation remain uncertain. Research led by Carina Hanashima from the RIKEN Center for Developmental Biology has now uncovered how feedback between cells, as well as molecular factors, helps shape cortical development during mouse embryogenesis.

The cortex is made up of layers of interconnecting cells that are produced in a particular order from progenitor cells. The relatively cell-sparse outer layer is formed first, then the dense deep layer, and finally the tightly packed upper layer. Hanashima and her colleagues were interested to discover exactly how the various layers form, so they created a mouse model that enabled them to control the expression of a particular protein, Foxg1, known to be involved in cortical development.

The Foxg1 gene, if switched on toward the end of embryogenesis after the outer layer of neurons has formed, triggers the production of deep-layer neurons, followed by upper-layer neurons (Fig. 1). The researchers found that it does this by repressing the activity of another gene, called Tbr1, in the outer-layer neurons.

Say you live across from a bakery. Sometimes you are hungry and therefore tempted when odors waft through your window, but other times satiety makes you indifferent. Sometimes popping over for a popover seems trouble-free but sometimes your spiteful ex is there. Your brain balances many influences in determining what you’ll do. A new MIT study details an example of this working in a much simpler animal, highlighting a potentially fundamental principle of how nervous systems integrate multiple factors to guide food-seeking behavior.

All animals share the challenge of weighing diverse sensory cues and internal states when formulating behaviors, but scientists know little about how this actually occurs. To gain deep insight, the research team based at The Picower Institute for Learning and Memory turned to the C. elegans worm, whose well-defined behavioral states and 302-cell nervous system make the complex problem at least tractable. They emerged with a case study of how in a crucial olfactory neuron called AWA, many sources of state and sensory information converge to independently throttle the expression of a key smell receptor. The integration of their influence on that receptor’s abundance then determines how AWA guides roaming around for food.

“In this study, we dissected the mechanisms that control the levels of a single olfactory receptor in a single olfactory neuron, based on the ongoing state and stimuli the animal experiences,” said senior author Steven Flavell, Lister Brothers Associate Professor in MIT’s Department of Brain and Cognitive Sciences. “Understanding how the integration happens in one cell will point the way for how it may happen in general, in other worm neurons and in other animals.”

Summary: The TOB gene plays a significant role in reducing depression, anxiety, and fear in mouse models. The findings could have positive implications for developing new treatments for disorders associated with psychiatric stress.

Source: OIST

First characterized in Prof. Tadashi Yamamoto’s former lab in Japan in 1996, the gene Tob is well known for the role it plays in cancer. Previous research has also indicated that it has a hand in regulating the cell cycle and the body’s immune response.

The activity of neurons has been measured in a slice of mouse tissue using a quantum diamond sensor – and it might one day enable a new type of non-invasive brain scanning.

Summary: Determining the structure of vitronectin, a protein implicated in age-related macular degeneration and some neurodegenerative disorders, and using pressure to alter the protein shape may help in the development of new treatments for AMD.

Source: Sanford Burnham Prebys.

Research led by Sanford Burnham Prebys professor Francesca Marassi, Ph.D., is helping to reveal the molecular secrets of macular degeneration, which causes almost 90% of all age-related vision loss.

Animal studies on great apes have long been banned in Europe for ethical reasons. For the question pursued here, organoids (three-dimensional cell structures a few millimeters in size that are grown in the laboratory) are an alternative to animal experiments. These organoids can be produced from pluripotent stem cells, which then differentiate into specific cell types, such as nerve cells. In this way, the research team was able to produce both chimpanzee brain organoids and human brain organoids. “These brain organoids allowed us to investigate a central question concerning ARHGAP11B,” says Wieland Huttner of the MPI-CBG, one of the three lead authors of the study published in EMBO Reports.

“In a previous study we were able to show that ARHGAP11B can enlarge a primate brain. However, it was previously unclear whether ARHGAP11B had a major or minor role in the evolutionary enlargement of the human neocortex,” says Wieland Huttner. To clarify this, the ARGHAP11B gene was first inserted into brain ventricle-like structures of chimpanzee organoids. Would the ARGHAP11B gene lead to the proliferation of those brain stem cells in the chimpanzee brain that are necessary for the enlargement of the neocortex?

“Our study shows that the gene in chimpanzee organoids causes an increase in relevant brain stem cells and an increase in those neurons that play a crucial role in the extraordinary mental abilities of humans,” said Michael Heide, the study’s lead author, who is head of the Junior Research Group Brain Development and Evolution at the DPZ and employee at the MPI-CBG.

One of the major current theories of consciousness is that brain oscillations, also called brain waves, correlate with specific mental states. It is the synchronous waves from different regions, that is, those that are beating at the same rate, that are believed to be important for the connection of different brain regions. Brain waves have been observed for more than a hundred years, but it is still not clear exactly what they are and what they have to do with the function of the brain and the mind.

Oscillations in the brain occur because of an interplay between two forces, such as stimulation and inhibition. This dynamic can either come from two different cortical layers or a cortical and subcortical layer. Feedback properties affect the oscillations by either continuing the give and take of the two forces or changing them in various ways. Even with no outside input, the brain creates spontaneous oscillations; a well-known example is the one, connected to the thalamus and cortex, that occurs during sleep. Currently, it is believed that these oscillations help to synthesize and filter the previous day’s memories. While these oscillations are associated with sleep, most other brain oscillations are not clearly correlated with mental states.