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Development of the vertebrate central nervous system...
 Our laboratory uses a variety of approaches to investigate how integrated neuronal systems are established during the development of the vertebrate central nervous system. For us, this requires an understanding of how early patterning events relate to the molecular and morphological development of individual neurons and how this varies between species.
We also have a strong commitment to public engagement
What we do
Using the rhombic lip as a model system, we have employed time-lapse confocal microscopy of GFP labelled cells, fate-mapping and genetic approaches to determine how a diversity of neurons with intricately patterned connections is generated.
Our studies impact a range of human disorders, but we have a specific current interest in Autistic Spectrum Disorder as part of an MRC funded collaboration with Dr. Albert Basson (MRC/Craniofacial) and Dr. Cathy Fernandes (IoP).
Investigating the rhombic lip organizer (funded by the BBSRC)
 The rhombic lip lies at the boundary between neural tissue and non-neural tissue. Signals from the latter to the former are important in specifying the cells that are born at the rhombic lip. We have found that the rhombic lip also signals to the roof plate, patterning the development of the choroid plexus. We have investigated how these signals rely on Delta-Notch mediated cell interactions. Currently we are looking at how these interactions translate into cellular organization in zebrafish, in collaboration with Professor Jon Clarke (MRC Centre)
Broom ER, Gilthorpe JD, Butts T, Campo-Paysaa F and Wingate RJ (2012). The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development. Development 139(22): 4261-70
Evolution of the cerebellum and cerebellar-like systems (funded by the Royal Society)
 While the ground plan for the development of the central nervous system is similar throughout all vertebrates, the final shape and size of its adult components can be highly variable. Perhaps the most variable of all central nervous system structures is the cerebellum, a centre of unconscious movement control in mammals, which shows an enormous variety of scale and form. However, at its core, the synapse between the granule cell (which channels the majority of inputs to the cerebellum) and the Purkinje cell (its output) is remarkably constant . Furthermore this synaptic motif is found in a number of cerebellar-like systems. We are investigating both the origins of cerebellar diversity and the gene network that defines the relatively invariant, core synaptic arrangement. To do this we are looking at gene function and cell migration in a number of species: Mississippi paddlefish, shark, zebrafish, frog and chick. We are grateful for past support for this project from the BBSRC.
Chaplin N, Tendeng C and Wingate RJ (2010). Absence of an external germinal layer in zebrafish and shark reveals a distinct, anamniote ground plan of cerebellum development. J Neurosci 30, 3048-57. Butts T, Chaplin N and Wingate RJ (2010). Can Clues from Evolution Unlock the Molecular Development of the Cerebellum? Mol Neurobiol.
Retinoic acid and dorsal hindbrain development (funded by the Wellcome Trust)
 Vitamin A is broken down in the body to make retinoic acid in the choroid plexus and other tissues. This biologically active molecule has multiple, important roles in normal embryonic development. Too much or too little retinoic acid can have serious consequences for the developing foetus. In humans, damaging effects are concentrated in a few important groups of neurons in the cerebellum and hindbrain. We are currently trying to understand how retinoic acid signals from the choroid plexus influence the generation of neruosn from the rhombic lip, in collaboration with Professor Malcolm Maden (University of Florida).
Wilson LJ, Myat A, Sharma A, Maden M and Wingate RJ (2007). Retinoic acid is a potential dorsalising signal in the late embryonic chick hindbrain. BMC Dev Biol 7, 138.
AlumniDr. Thomas Butts Dr. Emma Broom Dr. Natalie Chaplin Dr. Mark Eddison Leah Toole Moheb Costandi |
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