Brain patterning: A major focus for our research has been to elucidate the signalling pathways that establish anterior-posterior, dorsoventral and left-right pattern in the brain.  For instance, we showed that mutations and manipulations that modulate Wnt signalling within the neural plate change the allocation of regional fates in both forebrain and eyes. Furthermore, our studies of morphogenesis and cell movements led to the demonstration of critical roles for a non-canonical Wnt-PCP pathway during both mesodermal and CNS morphogenesis. 

Eye development:  One current focus for our research is to resolve the genetic bases of, and cellular mechanisms underlying, eye specification and morphogenesis with a linked goal of understanding why MAC (microphthalmia, anopthalmia and coloboma) phenotypes can arise when eye formation is disrupted. One approach is to use high-resolution time-lapse imaging to characterize the cell and tissue movements accompanying eye formation and to couple this with genetic screens to identify mutations that disrupt eye formation.

Brain asymmetry: Research from the our lab has helped to establish the zebrafish as by far the leading vertebrate model to study the development of brain asymmetry.   We have shown that breaking of symmetry and allocation of handedness to the asymmetry are separable processes and that Nodal, Wnt and Fgf pathways together break symmetry and determine its laterality.   Complementing genetic studies, his team are analyzing the developmental neuroanatomy of the brain, particularly with respect to asymmetric circuitry.   For instance, we have shown that the left and right habenular nuclei project to different regions of their target nucleus, and that for individual neurons, left-right asymmetry is manifest as differences in axon terminal morphology and targeting.  

These neuroanatomical studies underpin research that aims to link circuitry to neuronal activity and behaviour.   One major challenge is to identify complex behaviours that are sufficiently robust to be amenable to both genetic and neuroanatomical interrogation.  To this end, we, and others, are developing assays for simple learning and fear responses and social interactions in fry.  Coupled to analysing behaviour, we are using genetic/optogenetic approaches to interrogate neuronal activity in lateralised brain nuclei.  We have recently found that the left and right habenulae respond to different sensory stimuli and that loss of brain asymmetry impairs the ability to respond to such stimuli.  The long-term goal of our research is to be able to move seamlessly from genes through developmental mechanisms to circuits and behaviour in the intact developing animal. 

The UCL zebrafish website will give you more details of some of our lab’s research projects and publications (www.ucl.ac.uk/zebrafish-group/)