Molecular neurobiology

Molecular neurobiology

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Group Leader

Dario Bonanomi

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Our ability to sense, move, think and remember relies on precise patterns of connections set during embryonic development by billions of neurons in the brain and spinal cord that elaborate highly branched processes and send long axonal projections to contact their synaptic targets. Because nerve cells do not divide and proliferate, most of them are as old as we are – therefore each neuron needs to preserve its specialized morphology and connections for the entire life of the organism, coping with aging, injury and disease. Our laboratory explores the cellular and molecular underpinnings of neuronal connectivity; we make use of mouse genetics, cellular assays, biochemistry and imaging to study the developmental wiring, homeostasis and repair of neural circuits in the vertebrate nervous system, with emphasis on spinal motor neurons that control body movements and are selectively lost in amyotrophic lateral sclerosis and other neurological disorders. Research in the laboratory addresses the signaling mechanisms that underlie neuronal morphogenesis and patterning of axonal projections. Another focus is on the crosstalk between neurons and blood vessels, and its contribution to the assembly and maintenance of neural circuits.

Research Activity

Neuronal guidance and connectivity in the spinal motor system
A central interest of the laboratory is to unmask key molecular determinants that underlie transition from exuberant axon growth and pathfinding during development to later stabilization, maintenance and ultimately regression of connections as occurs in aging or disease. We combine in vivo (transgenic mice, chick embryos) and in vitro (primary neurons, stem cells) models integrated with proteomic and gene expression analysis to extract mechanistic insights on how individual signaling pathways function and collaborate to direct the axonal trajectories of motor neurons that connect to distant muscle targets.

Neurovascular communication and neuronal wiring
The high-energy cost of sustaining complex interconnections makes neurons critically dependent on vascular supply of nutrients and oxygen, as reflected in the expansive vascularization of the nervous system and precise alignment of nerves and blood vessels. What remains unclear is how the neurovascular link is established, so that the vascular network matches the functional requirements of specific neuronal populations. Our work seeks to define both the developmental signals that instruct neurovascular crosstalk and the way this tight association is maintained during circuit remodeling. We study mouse models in which this crosstalk is disrupted by gene mutations, and take advantage of cell-specific transgenic reporters that reveal neurovascular interactions in intact tissues to uncover the molecular programs that link neuronal connectivity and vascularization of the nervous system.