James Briscoe: Projects

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 we are elucidating the genetic networks that regulate the specification and differentiation of this cell type.

The serotonergic system in the brainstem

The serotonergic system in the brainstem

Serotonergic neurons are sequentially generated from a bipotent progenitor pool that first generates visceral motor neurons. The activity of a set of transcription factors, including Foxa2 and Acsl1 are expressed in serotonergic progenitors and regulate the serotonergic differentiation programme. We are now beginning to piece together the pathways that link progenitor specification with the acquisition of serotonergic traits. 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. 

Selected publications

Jacob J, Ribes V, Moore S, Constable SC, Sasai N, Gerety SS, Martin DJ, Sergeant CP, Wilkinson DG, Briscoe J. (2014). Valproic acid silencing of ascl1b/Ascl1 results in the failure of serotonergic differentiation in a zebrafish model of fetal valproate syndromeDis Model Mech. 7:107-17

Jacob J, Kong J, Moore S, Milton C, Sasai N, Gonzalez-Quevedo R, Terriente J, Imayoshi I, Kageyama R, Wilkinson DG, Novitch BG, Briscoe J. (2013) Retinoid acid specifies neuronal identity through graded expression of Ascl1Curr Biol. 23:412-8.

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 hindbrainDevelopment 136, 2477-2485

 

James Briscoe

James Briscoe

james.briscoe@crick.ac.uk
+44 (0)20 379 61388

  • Qualifications and history
  • 1996 PhD Imperial Cancer Research Fund/Kings College, London, UK
  • 1996 Post doctoral fellow Columbia University, New York, USA
  • 2000 Group Leader, Medical Research Council National Institute for Medical Research, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK