MRC National Institute for Medical Research, London
Science for Health
James Briscoe group project:
Development of the serotonergic system
Located in the brainstem, serotonergic neurons are a clinically important neuronal subtype that are generated in response to high levels of Shh signalling. Serotonergic neurons innervate virtually the entire CNS and regulate numerous physiological and behavioural processes, including mood, appetite, locomotion and cognition. Consequently, abnormal serotonergic function is implicated in several common neurological and psychiatric diseases including autism, depression, movement and headache disorders. Knowledge of the molecular programmes that control the differentiation of serotonergic neurons would provide greater understanding of the pathophysiological mechanisms associated with these conditions. To this end, John Jacob, a clinical fellow in the lab is elucidating the genetic networks that regulate the specification and differentiation of this cell type.
Serotonergic neurons are sequentially generated from a bipotent progenitor pool that first generates visceral motor neurons. Sequential cross-repression between two transcription factors, Foxa2 and Phox2b expressed in the common progenitor triggers the temporal identity switch, and instructs the serotonergic differentiation program. We are now beginning to piece together the pathways that link progenitor specification with the acquisition of serotonergic traits, in particular neurotransmitter identity. Currently, we are investigating how the spatial distribution of serotonergic neurons is regulated, with a view to understanding the molecular mechanism of serotonergic dysgenesis in certain autism spectrum disorders.
The serotonergic system in the brainstem
Click image to view at full-size
Selected publications
- Jacob J, Storm R, Castro DS, Milton C, Pla P, Guillemot F, Birchmeier C and Briscoe J (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 - Jacob J, Ferri AL, Milton C, Prin F, Pla P, Lin W, Gavalas A, Ang S-L and Briscoe J (2007)
Transcriptional repression coordinates the temporal switch from motor to serotonergic neurogenesis.
Nature Neuroscience 10, 1433-9 PubMed abstract
Briscoe group
Recent publications
Research projects
- Dynamics of Shh signalling and gene expression
- Coordinating patterning and growth
- Elucidation of the transcriptional network
- Visualising gene expression
- Development of the serotonergic system
Briscoe biography
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