Prof John Parnavelas
Neuronal migration in the forebrain
Cortical Interneuron Migration
Work in our laboratory has, for many years, focused on the origin and migration of the neurons that make up the mammalian cerebral cortex.
The neocortex is the part of the brain involved in high-level cognitive functions and its expansion is regarded as a major evolutionary modification that led to the emergence of intelligence. These processes are achieved through circuits comprised of two classes of neurons organised in layers: excitatory pyramidal neurons and inhibitory interneurons. Perturbations in the development of these cortical circuits can lead to neurological disorders. Recent studies indicate a role for interneurons in the neuropathology and development of epilepsy, schizophrenia, autism and mental retardation. Thus, understanding the molecular mechanisms that control the generation and migration of interneurons and their roles in cortical function is of significant clinical relevance and therapeutic importance.
Our current studies focus on exploring the functions of molecules involved in forebrain interneuron migration, specifically several classes of chemorepulsive ligands and their receptors. Examples of such molecules include Slit-Robo and Semaphorin/Neuropilin-Plexin families as well as some of their downstream signalling partners (e.g. Limk2). We have also recently carried out microarray studies which identified candidate novel molecules that showed differential expression between dorsal and ventral forebrain, as well as between different cortical interneuron streams, suggesting these novel genes may play distinct roles in interneuron migration either within specific forebrain compartments or within distinct migratory streams. In our studies, we utilise transgenic mouse lines as well as loss- and gain-of-function approaches in brain slice and explant cultures.
Development of Cardiac Innervation
In combination with the interneuron migration projects, we are also exploring the roles of some of the same molecules involved in forebrain neuron migration in the development of the innervation of the heart. This project focuses on the Slit-Robo signalling pathway, which is mainly known for its role in axon guidance.
The innervation is crucial for normal functioning of the heart, as it modulates cardiac activity by regulating the activity of the sinus and atrioventricular nodes, conduction of the cardiac impulse and the strength of atrial and ventricular contraction. Sympathetic nerves are responsible for increase of the heart rate and force of contraction, whereas parasympathetic nerves achieve the opposite effect. Cardiac innervation density is altered in congenital heart disease, heart failure, diabetic neuropathy and myocardial ischemia. Despite the severity of these diseases, knowledge about the developmental and regulatory mechanisms underlying decisions for guiding nerves to specific parts of the heart is still limited.
Our project focuses on how the different ligands and receptors of the Slit-Robo signalling pathway tightly control which nerves are allowed to enter the heart during embryonic development.
- John Parnavelas E-mail: firstname.lastname@example.org
- William Andrews (Postdoctoral Research Fellow); E-mail: email@example.com
- Mathilda Mommersteeg (Postdoctoral Research Fellow): firstname.lastname@example.org
- Fani Memi (Ph.D. Student): email@example.com
- Mason Yeh (Ph.D. Student): firstname.lastname@example.org
- Eleni Doumou (Student): email@example.com
- Elisa Marzorati (Student): firstname.lastname@example.org
Department of Cell and Developmental Biology
University College London
21 University Street
Tel. Prof. Parnavelas: +44-20-3108-2204
Tel. lab: +44-20-3108-2426
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Page last modified on 16 apr 13 13:22 by Sonja Van Praag