MRC National Institute for Medical Research, London
Science for Health
New component in brain neurons identified
02 July 2009
Neurons in the central nervous system communicate with each other by releasing chemical messengers, called neurotransmitters, at specialised junctions, termed synapses. These molecules are synthesised from precursors by biosynthetic enzymes in multi-step biochemical pathways. The neurotransmitters profoundly affect how the post-synaptic neurons respond, and are therefore the arbiters of brain function. The enzyme-coding genes which make the neurotransmitters are controlled by transcription factors and it is these transcription factors that ultimately dictate the choice of neurotransmitter.
Two clinically important neuronal classes that regulate many brain functions, including cognition, pain perception, movement and appetite, utilise serotonin or noradrenaline as neurotransmitters. Dysfunction of these neurotransmitter systems has been implicated in the pathophysiology of several common neurological and psychiatric disorders, such as Parkinson's disease, anxiety and depression, autism, sleep and eating disorders. Therefore, understanding how the synthesis of these important chemicals is regulated during development could provide insight into disease mechanisms.
John Jacob, James Briscoe (pictured) and colleagues have identified two key molecular players, the transcription factors Insm1 and Ascl1, that together regulate the choice of neurotransmitter in the two types of neurons. Previous work by several groups had shown that Ascl1 is important for the differentiation of these neuronal subtypes. In collaboration with Francois Guillemot's group at NIMR and Carmen Birchmeier's lab at the Max Delbruck Centre in Berlin, Dr Jacob discovered that Ascl1 and Insm1 regulate distinct enzyme-coding genes in different ways in the two neuronal subtypes. Remarkably, in the fly brain similar strategies are used to regulate the differential expression of peptidergic transmitters.
Dr Jacob said:
This work brings us a step closer to understanding how the extremely complex genetic programs that are initiated in embryonic brain cells control the selection of neuronal properties. Our findings may provide geneticists with novel factors to investigate for the origins of diseases which affect these types of neurons.
Original article
The research findings are published in full in:
John Jacob, Robert Storm, Diogo S. Castro, Christopher Milton, Patrick Pla, François Guillemot, Carmen Birchmeier, and James Briscoe. (2009)
Insm1 (IA-1) is an essential component of the regulatory network that specifies monoaminergic neuronal phenotypes in the vertebrate hindbrain
Development 136:2477-2485. Pubmed abstract
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