Study maps neurogenetics of dendritic growth and formation.

A neuron is an electrically excitable cell that processes and transmits information through electrical and chemical signals in the brain. These signals between neurons occur via synapses, which connect to other brain cells to form neural networks.  A healthy neuron consists of a cell body (soma), dendrites, and an axon.  Dendrites are thin structures that arise from the cell body, often extending for hundreds of micrometres and branching multiple times, giving rise to a complex dendritic tree.  And just as a healthy tree can be judged by its canopy, so too can a healthy neuron be judged by its dendritic branches.  However, it is unclear what causes dendrites to grow, and where those instructions to grow come from.  Now, a study from researchers at the University of Iowa identifies a group of genes associated with neurons, which help regulate dendrites’ growth. The team state that these genes, called gamma-protocadherins, must be an exact match for each neuron for the cells to correctly grow dendrites.  The opensource study is published in the journal Cell Reports.

Previous studies show that the human brain is filled with neurons. Scientists think adults have 100 billion brain cells, each in close proximity to others and all seeking to make contact through their axons and dendrites. It is known that the denser a neuron’s dendritic network, the more apt a cell is to be in touch with another and aid in passing signals.  Gamma-protocadherins act like molecular Velcro, binding neurons together and instructing them to grow their dendrites.  The current study manipulates the expression of gamma-protocadherins adhesion molecule isoforms in the mouse cerebral cortex to demonstrate that the complexity of a neuron’s dendritic arbor is promoted by local homophilic interactions with other neurons and with astrocytes.

The current study provided a developing brain cell in a mouse the same gamma-protocadherin as in surrounding cells; when they did, the cells grew longer, more complex dendrites.  Results show that when the lab outfitted a mouse neuron with a different gamma-protocadherin than the cells around it, dendritic growth was stunted.

The group explain that the mice expressed the same type of gamma-protocadherin in neurons in the cerebral cortex, a region of the brain that processes language and information. Data finding show that after five weeks, the neurons had sizeable dendritic networks, indicative of a healthy, normally functioning brain.  Results show that when they turned on a gamma-protocadherin gene in a neuron different from the gamma-protocadherin gene with the cells surrounding it, the mice had limited dendrite growth after the same time period.

The researchers state that this is important because human neurons carry up to six gamma-protocadherins, meaning there are many combinations potentially in play. They go on to note that it seems the dendrite growth signal only happens when neurons carrying the same gamma-protocadherin gene pair up.

Results show that star-looking cells called astrocytes, which are glial cells that help to bridge the gap between neurons and speed signals along, also play a role in neurons’ dendritic development.  Data findings show that when the molecular binding between an astrocyte and a neuron is an exact match, the neurons grow fully formed dendrites, the researchers report.

The team surmise that their data indicate gamma-protocadherins act locally to promote dendrite arborization via homophilic matching and confirm that connectivity in vivo depends on neurogenetic interactions between neurons and between neurons and astrocytes.  For the future, the researchers state that their findings may offer new insight into disrupted dendrite arborization as seen in the brains of people with autism and schizophrenia, as well as help researchers better understand brain development in babies born prematurely.

Source: University of Iowa