Mechanism explains complex brain wiring

11 June 2014
​How neurons are created and integrate with each other is one of biology’s greatest riddles. Researcher Dietmar Schmucker from VIB-KU Leuven unravels a part of the mystery in Science magazine. He describes a mechanism that explains novel aspects of how the wiring of highly branched neurons in the brain works. These new insights into how complex neural networks are formed are very important for understanding and treating neurological diseases.

Neurons, or nerve cells
It is estimated that a person has 100 billion neurons, or nerve cells. These neurons have thin, elongated, highly branched offshoots called dendrites and axons. They are the body’s information and signal processors. The dendrites receive electrical impulses from the other neurons and conduct these to the cell body. The cell body then decides whether stimuli will or will not be transferred to other cells via the axon.

The brain’s wiring is very complex. Although the molecular mechanisms that explain the linear connection between neurons have already been described numerous times, little is as yet known about how the branched wiring works in the brain.

The connections between nerve cells
Prior research by Dietmar Schmucker and his team lead to the identification of the Dscam1 protein in the fruit fly. The neuron can create many different protein variations, or isoforms, from this same protein. The specific set of isoforms that occurs on a neuron’s cell surface determines the neuron’s unique molecular identity and plays an important role in the establishment of accurate connections. In other words, it describes why certain neurons either come into contact with each other or reject each other.

Recent work by Haihuai He and Yoshiaki Kise from Dietmar’s team indicates that different sets of Dscam1 isoforms occur inside one axon, between the newly formed offshoots amongst each other. If this was not the case, then only linear connections could come about between neurons. These results indicate for the first time the significance of why different sets of the same protein variations can occur in one neuron and it could explain mechanistically how this contributes to the complex wiring in our brain.

Clinical impact
Although this research was done with fruit flies, it also provides new insights that help explain the wiring and complex interactions of the human brain and shine a new light on neurological development disorders such as autism. Thorough knowledge of nerve cell creation and their neural interactions is considered essential knowledge for the future possibility of using stem cell therapy as standard treatment for certain nervous system disorders.

Questions
Given that this research can raise many questions, we would like to refer your questions in your report or article to the email address that the VIB has made available for this purpose. All questions regarding this and other medical research can be directed to: patients*Replace*With*At*Sign*vib.be.

Relevant scientific publication
The above-mentioned research was published in the prominent magazine Science (Haihuai and Yoshiaki et al., Cell-Intrinsic Requirement of Dscam1 Isoform Diversity for Axon Collateral Formation). 10.1126/science.1251852.

Research team
This research was conducted by the research team headed by Dietmar Schmucker, who leads a research group at the VIB Vesalius Onderzoekscentrum, KU Leuven (Flemish Institute of Biology Vesalius Research Centre, Catholic University of Leuven).

Financing
This research was co-financed by:
VIB start-up funding FWO; BELSPO IUAP VII-20,; JSPS Postdoctoral Fellowship, HFSP Long-Term Fellowship, FWO PhD. Fellowship, Swiss National Science Foundation Postdoctoral Fellowship, Boehringer Ingelheim Fonds PhD Fellowship


highly branched neuron
©VIB 2014