General

The overall goal of our research program is to investigate the involvement of proteinases and signalling neuropeptides, in neural circuit development and in neuronal survival, plasticity and regeneration. Several mouse and zebrafish models (see below), various transgenic technologies (knock-out mice, knock-down or overexpression through plasmid electroporation, morpholino-technology, etc.) and in vivo, ex vivo and in vitro experiments are being used to define the importance of such molecules in neuronal patterning/survival, in axon outgrowth/regeneration and in neuroplasticity, and to determine underlying mechanisms and substrate interactions.

Molecules under study

Our research is largely focused on the involvement of matrix metalloproteinases (MMPs) in central nervous system (CNS) physiology and pathology. MMPs are proteinases that cleave structural elements of the extracellular matrix and many molecules involved in signal transduction, thereby contributing to a variety of biological processes, both under physiological and pathological conditions. Besides a proven detrimental role in neurological diseases, a beneficial role for MMPs in key physiological and regenerative brain events is emerging. In pathological circumstances, MMP upregulation can amplify blood-brain barrier dysfunction, demyelination, neuroinflammation and neurotoxicity. However, MMP inhibition as a therapeutic strategy remains difficult, as non-selective inhibitors might also inhibit the neuroprotective or reparative functions of specific MMPs. Therefore, the challenges for a better understanding of the MMP biology are considerable. It is important to define which MMPs are involved in a particular physiological or pathological process/state, how they achieve their effects, and which function each MMP has in the overall scheme.
Additionally, we have a major interest in neuropeptide signaling in the brain. Neuropeptides are small regulatory proteins exerting key roles in many physiological processes within and outside the CNS. Neuropeptides exert multiple actions in developing and adult organisms and have also been implicated in axon growth and regeneration. Despite many years of research, there is still limited knowledge on the role of peptides in brain physiology and pathology. We intend to identify novel bio-active neuropeptides affecting axonal outgrowth and regeneration in the CNS. 

Model systems under study

Correct wiring of neuronal circuits in the developing brain relies on the precise spatial positioning of neurons and their axons. Several extracellular molecules are known to behave as guidance cues for neuronal and axonal patterning. In addition, several of these guidance molecules have shown important roles in adult brain plasticity or neural circuit regeneration after damage to the nervous system. We have an ample interest in investigating neuronal patterning, synaptogenesis and plasticity in the developing and injured cerebellum and use mouse models to study morphogenesis and remodelling of the cerebellum (Inge Van Hove - Mieke Verslegers). Additionally, we focus on analysing axon outgrowth and guidance during developmental and regenerative processes. In order to study developmental axon navigation, we use a mouse model for commissural axon pathfinding in the embryonic spinal cord (Djoere Gaublomme). We are also interested in the development of the retinotectal circuit and in the survival/regeneration of the retinal ganglion cells (RGC) and their axons after optic nerve neuropathy. On the one hand this research line focuses on investigating the molecular signalling pathways involved in retinotectal axon pathfinding during development and after optic nerve axotomy in zebrafish (Els Janssens - Stitipragyan Bhumika - Tom Buyens). Further, to explore the importance of molecules for RGC survival and axonal outgrowth, we also make use of ex vivo cultures of retinal explants, harvested from postnatal mice (Tom Buyens).

Another branch of our research focuses on neurodegenerative diseases affecting the visual system, such as glaucoma. Glaucoma is a progressive neurodegenerative disease and, as a leading cause of blindness, an increasingly important public health concern due to the aging world population. We investigate molecules and processes contributing to RGC survival using a microbead-induced glaucoma model in the mouse (Lies De Groef - Djoere Gaublomme). In addition, we study the involvement of the brain in glaucoma disease progression and its possible role in providing neuroprotection of the RGCs (Eline Dekeyster).