Health
Studies reveal how gene regulatory mechanisms define the identity of developing brainstem neurons
A recent study at the University of Helsinki reveals how gene regulatory mechanisms define the identity of developing neurons in the brainstem. Researchers have also shown that failure to differentiate brainstem neurons leads to behavioral abnormalities such as hyperactivity and attention deficit.
Although the mammalian brain is large, its state of activity is controlled by far fewer neurons. Many of these are located in the brainstem, an evolutionarily conserved part of the brain that controls mood, motivation, and motor activity. What are brainstem neurons? How do they develop in the embryonic brain? How are these developmental deficiencies reflected in brain activity and behavior?
A research group led by Professor Juha Partanen of the Faculty of Bioenvironmental Sciences, University of Helsinki, addresses these issues by studying gene regulation in the brainstem of the embryo.
The phenotype of neurons is mostly already determined in the early stages of the embryo. We have shown how specific selector genes, which are expressed shortly after the onset of neuron differentiation and control the activity of other neuron-specific genes, determine the identity of developing neurons.
Over the past few years, we have provided us with a very powerful tool for studying gene expression in individual cells. By analyzing the gene products of embryonic brain cells, we can follow the differentiation pathways of neurons and find out exactly what happens when developing cells follow different pathways.
The differentiation pathway diverges to produce a remarkable neuronal diversity that underlies brain function. According to gene expression-based identities, immature neurons find their location in the brain and make contact with other components of the neural circuit.
What if the gene expression label points in the wrong direction and the developing neuron is misrouted? In the brainstem, this has serious consequences for both brain function and behavior.
Under these circumstances, we studied mice with an imbalance in neuronal differentiation that activates or inhibits the dopaminergic and serotonergic neurotransmitter systems. These mice are hyperactive and impulsive. There are changes in reward perception and learning. Hyperactivity can be reduced. With drugs used to treat human attention and hyperactivity disorders, “Partanen reveals.
In short, Partanen shows:Despite active research, the developmental basis of many human behavioral disorders is not yet well understood. It is not yet known whether the human counterparts of the neurons we studied are involved in these deficits.Nonetheless, from a behavioral regulatory perspective, this particular group of neurons is very important and there is still much to learn about them... “
Source:
Journal reference:
Morero, F. , et al. (2020) Molecular fingerprinting and developmental regulation of covered GABAergic and glutamatergic neurons from the anterior-posterior brain. Cell reports.. doi.org/10.1016/j.celrep.2020.108268..
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