The use of stem cells to produce neurons for treating neurological diseases depends on a deep understanding of how neurons differentiate during embryonic and fetal life. Research in our laboratory is focused on two main topics: 1) the regional patterning and differentiation of neurons and the development of functional connections between them that give rise to defined sensorimotor circuits, and 2) neuronal differentiation of human adult somatic stem cells and of human pluripotent stem cells, as a means of generating the neurons that make up these circuits. The research group consists of 15 scientists, postdocs, PhD students and technicians. Our technical expertise lies in neuronal tract tracing, the characterization of neuronal differentiation at the molecular (mRNA and protein) and structural level, the use of electrophysiological and optical recording techniques to assess functional synaptic connectivity, and more recently in vivo MRI-based tracking of human stem cells in animal models.
Our long term goal is to understand how specific sensorimotor circuits in the brain stem and spinal cord develop and how stem cells can be used both in potential replacement therapies for such conditions as spinal cord injury and as tools to better understand the molecular and cellular mechanisms underlying neuronal patterning, differentiation and synaptic coupling. We are focusing in particular on the neuronal circuits that mediate the descending control of spinal motor programs and the ascending control of eye movements, including vestibulospinal, reticulospinal and vestibulo-ocular projections.
- Development of mammalian and avian reticulospinal, vestibulospinal and vestibulo-ocular projections, including molecular characterization of projection neuron subpopulations and optical and electrophysiological recording of synaptic activation patterns.
- Anteroposterior and dorsoventral patterning of reticular and vestibular projection neurons, through fate-mapping and correlation with AP and DV patterning gene expression.
- Molecular, anatomical and physiological development of extraocular motoneurons.
Characterization of the molecular mechanisms underlying regulative regeneration in the embryonic spinal cord, wherein neural tissue spontaneously repairs itself through controlled proliferation and differentiation.
- Generation of neurons from human embryonic and adult somatic stem cells as a platform for developing regenerative treatments for spinal cord injury.
- First demonstration of the requirement of serotonin for animal locomotion (Glover and Kramer, Science, 1984).
- Invented the technique of retrograde labeling using conjugated dextrans, now used world-wide (Glover et al, J Neurosci Methods, 1986).
- First demonstration of clonal relationships giving rise to neuron columns in a laminar brain structure, and the progression from symmetric to asymmetric divisions in clones of neural stem cells (Gray et al, PNAS, 1988).
- First description of the development of an identified spinal interneuron in an amniote embryo (Eide and Glover, J Neurosci, 1996).
- Demonstration of a retinoid-dependent segmental patterning of sympathetic preganglionic neurons (Forehand et al., PNAS, 1998).
- Segmental analyses of reticulospinal and vestibular projection neurons in avians and mammals (Glover and Petursdottir, J Neurobiol, 1991; Diaz et al, Dev Biol 1998; Auclair et al, J Comp Neurol, 1999; Pasqualetti et al, J Neurosci, 2007).
- First demonstration of an in vivo differentiation of adult human non-neural somatic stem cells to neurons (Sigurjonsson et al, PNAS, 2005).
- First characterization using dynamic imaging methods of the emergence of an entire polysynaptic reflex pathway in a vertebrate (Glover et al, submitted).
Filippo Rijli, Friedrich Miescher Institute, Switzerland
Sascha du Lac, Salk Institute, USA
Carmina Díaz, Universidad de Albacete, Spain
Susan Dymecki, Harvard University, USA
Jeff Lichtman, Harvard University, USA
Estelle Gauda, Johns Hopkins University, USA
Bernd Fritzsch, University of Iowa, USA
Katsushige Sato, Komazawa Women's University, Japan
Yoko Momose-Sato, Kanto Gakuin University College, Japan
Szokol K, Glover JC, Perreault MC (2011) Organization of functional synaptic connections between medullary reticulospinal neurons and lumbar descending commissural interneurons in the neonatal mouse. J Neurosci 31:4731-4742.
Boulland JL, Halasi G, Kasumacic N, Glover JC (2010) Xenotransplantation of human stem cells into the chicken embryo. J Vis Exp, Jul 11;(41). pii: 2071. doi: 10.3791/2071.
Kasumacic N, Glover JC, Perreault MC (2010) Segmental patterns of vestibular-mediated synaptic inputs to axial and limb motoneurons in the neonatal mouse assessed by optical recording. J Physiol 588:4905-4925.
Szokol K, Glover JC, Perreault MC (2008) Differential origin of reticulospinal drive to motoneurons innervating trunk and hindlimb muscles in the mouse revealed by optical recording. J Physiol 586:5259-5276.
Pasqualetti M, Díaz C, Renaud JS, Rijli F and Glover JC (2007) Fate-mapping the mammalian hindbrain: Segmental origins of vestibular projection neurons assessed using rhombomere-specific Hoxa2 enhancer elements in the mouse embryo. J Neurosci 27:9670-9681.
Sigurjonsson OE, Perreault MC, Egeland T, Glover JC (2005) Adult human hematopoietic stem cells produce neurons efficiently in the regenerating chicken embryo spinal cord. PNAS 102:5227-5232.
Glover JC (2000) The development of specific connectivity between premotor neurons and motoneurons in the brain stem and spinal cord. Physiological Reviews 80:615-647.
Auclair F, Marchand R, Glover JC (1999) Regional patterning of reticulospinal and vestibulospinal neurons in the hindbrain of rat and mouse embryos. J Comp Neurol 411: 288-300.
Forehand CF, Ezerman EB, Goldblatt J, Glover JC (1998) The segment-specific pattern of sympathetic preganglionic projections is altered by retinoids. PNAS 95:10878-10883.
Eide AL, Glover JC (1996) The development of an identified spinal commissural interneuron population in an amniote: the neurons of the avian Hofmann nuclei. J Neurosci 16:5749-5761.
Glover JC, Petursdottir G (1991) Regional specificity of developing reticulospinal, vestibulospinal, and vestibulo-ocular projections in the chicken embryo. J Neurobiol 22:353-376.
Gray GE, Glover JC, Majors J, Sanes JR (1988) Radial arrangement of clonally related cells in the chicken optic tectum: Lineage analysis with a recombinant retrovirus. PNAS 85:7356-7360.
Glover JC, Petursdottir G, Jansen JKS (1986) Fluorescent dextran-amines used as axonal tracers in the nervous system of the chicken embryo. J Neurosci Methods 18: 243-254.