Insights into the Infancy of Neurons

In two studies, Gaia Tavosanis and fellow researchers at the DZNE have looked on mechanisms governing growth of neurons in fruit flies. The results which have been published in Current Biology and Cell Reports provide insights into the impact of nutrition on neuronal development and the lipid metabolism of neurons. These investigations might shine new light on similar processes, which take place in humans during both the embryonic phase and childhood, when the foundations of neural networks are laid out.

It is estimated that there could be hundreds of thousands of different types of neurons in the adult human brain. Each type displays specific morphological and functional characteristics allowing it to connect appropriately within the circuits of the brain and to efficiently process information. In particular, input signals to neurons are collected by their large arborized “antennae”, which are called dendrites. “As a matter of fact, the shape of dendrites represents the most readily identifiable sign of diversity among neuronal types”, explains professor Gaia Tavosanis, who leads a research group at the DZNE’s Bonn site. “The need for function-related diversity among neurons is not restricted to humans, but conserved also for much simpler brains. At our lab we study these fundamental aspects in the model organism Drosophila melanogaster. That is the common fruit fly.”

Nutrition affects neuronal development

Neuronal variety results from the interplay of multiple developmental signals. Within the evolving brain different genes are progressively expressed to settle neuronal identity. “Evidence from vertebrate studies suggested environmental modulation of these intrinsic genetic programming. That’s the reason, we took a close looked at associated mechanisms”, says Giovanni Marchetti, a postdoc at the Tavosanis lab. The scientists concentrated on the “mushroom body” in the adult fly brain, an area involved in the formation and retrieval of memories, similarly to the more complex mammalian hippocampus.

Neurons develop from neural stem cells. As the researchers describe in “Current Biology”, they found that a major consequence of the genetic programming is to decorate these cells with a sensor for the hormonal signal monitoring the nutritional state of the animal. “The cells are then prepared to respond to the signal bringing the information that the animal has reached the appropriate nutritional level. This serves as a trigger indicating that the next neuronal type can now be produced. In other words: nutrition might affect the fate of neurons as it interacts with the intrinsic developmental program”, Marchetti explains.

A matter of “fat”

Once the identity is clarified, neurons have to evolve into their specific shape. “Growing the arborized dendrites requires large amounts of lipids, the main component of membranes”, says post doc researcher Anna Ziegler. In a study published in “Cell Reports”, Ziegler and colleagues found that a master regulator for fatty acid de novo synthesis, a protein called SREBP, is as a key player for dendrite expansion. In the fruit fly, they noticed that neurons lacking SREBP grew shorter and fewer dendrites. Furthermore animals harboring such aberrant neurons overreacted to natural stimuli, suggesting that the cells were hyperexcitable. Additionally, they observed progressive damaging of “axons”, the neuron’s long projections, at late developmental stages.

“It was known that an external supply of lipids provided by so-called glia cells supports neuronal growth. However, our research shows the importance of the neuron’s autonomous control of lipid metabolism. That is to say: neurons have to produce their own lipids to grow proper dendritic and axonal structures”, Ziegler explains.

Understanding the young brain

Tavosanis adds: “Disruption of neuronal networks during early phases of development can lead to disorders such as autism, schizophrenia or intellectual disability. Thus, knowledge about the basic cellular and molecular mechanisms that underlie neural circuit formation can help to understand such neurological disorders. This may pave the way for novel ways of treatment.”

Original publications
Cell-Autonomous Control of Neuronal Dendrite Expansion via the Fatty Acid Synthesis Regulator SREBP.
Anna B. Ziegler, Christoph Thiele, Federico Tenedini, Mélisande Richard, Philipp Leyendecker, Astrid Hoermann, Peter Soba and Gaia Tavosanis.
Cell Reports, DOI: 10.1016/j.celrep.2017.11.069

Steroid Hormone Ecdysone Signaling Specifies Mushroom Body Neuron Sequential Fate via Chinmo.
Giovanni Marchetti and Gaia Tavosanis.
Current Biology, DOI: 10.1016/j.cub.2017.08.037