Mugnaini, Enrico, MD



Mugnaini, Enrico, MD




Office Phone

312-503 -4333

Office Fax

312-503 -7345


Cellular and Molecular Biology; Edgar F. Stuntz Professor


Searle 5-479 Chicago

Areas of Research

Cell Biology, Hearing Sciences, Motor Control, Systems Neuroscience

NU Scholar Profile

Recent Publications on PubMed

Current Research

Current Research

<strong>Neuronal Microcircuits in Cerebellum, Precerebellar Nuclei, Cell Class Specific Gene Expression, GABAergic Neurons.</strong>
My laboratory is interested in the mechanisms governing development, maintenance, and plasticity of specific neural cell classes, and in the principles of organization of nervous tissues in general. At present we are exploring the relationships between morphological and chemical phenotypes of special neuronal populations in motor and sensory pathways, and how these cellular and molecular features correlate with function at the cellular and system levels. Specifically, current projects deal with four topics: the cell biology and development of the unipolar brush cells of the cerebellar cortex, the small neurons of the cerebellar nuclei and their afferent synaptic connections, the expression of the actin-bundling protein espin in peripheral sensory neurons and cerebellar Purkinje cells, and the regulation of glutamate decarboxylase (the GABA synthetic enzyme) expression during development.
The unipolar brush cells (UBCs) receive a giant excitatory synapse from individual mossy fibers and this synapse offers a valuable model for studying neurotransmission and postsynaptic proteins in the central nervous system. There are two subsets of UBCs. The first subset expresses the calcium-binding protein calretinin and the second subset expresses the metabotropic glutamate receptor mGluR1a and the vesicular glutamate transporter VGLUT1. Current work intends to explore differential gene expression in the two subpopulations of UBCs. The UBC axons form a system of cortex-intrinsic glutamatergic mossy fibers that innervate granule cells and other UBCs.
Most of the small neurons in the cerebellar nuclei project to the inferior olive, which is the only source of cerebellar climbing fibers, and regulate the excitability of the olivary neurons and their electrotonic coupling. The inputs regulating their activity are still poorly known.
The espins are a family of Ca2+-insensitive actin-bundling proteins that are enriched in structures containing parallel actin fibers at the Sertoli cell-spermatogonial junction in the testis, in microvilli of intestinal and renal epithelial cell, in sterecilia of cochlear and vestibular hair cells, and in cerebellar Purkinje cells spines. The espin gene encodes several espin splice variants that are tissue and cell specific. In the testis, the predominant espin is a 110kD isoform, while in the inner ear a 50 kDa isoform of espin is present in the cochlear hair cell stereocilia, where it cross-links actin filaments in conjunction with the Ca2+-sensitive actin-bundling protein fimbrin. Purkinje spines have espin isoforms of intermediate lengths. The relative importance of espin and other acting bundling protein varies in different cells. In the inner ear, espin is thought to stabilize actin filaments and provide scaffolding for the stereocilia during the Ca2+ influx associated with mechanosensory function. A frame shift mutation in the c-terminal region of espin results in espin deficiency in jerker mutant mice and causes hair cell degeneration, deafness and disturbance of balance and posture. Male jerker mice, however, can mate and produce offspring, although they show reduced fertility. Jerker cerebellar Purkinje cells show subtle alterations of dendritic functions (Hartell et al., in preparation), but they maintain their characteristic shape and innervation (Sekerkova et al., 2003). Overall, jerker mice show numerous altered behavioral phenotypes and the jerker mutation presumably leads to syndromic effects yet to be characterized in full. Recently, espin mutations have been identified in a human family with major affection of innear ear functions ( ).
Recently, in collaboration with the group of G. Szabo and Z. Katarova we have introduced lines of GAD65-GFP mice that express the transgene in most of the GABAergic neurons in brain (manuscript in preparation).
Although mice and rats are our most common experimental animals, we often rely on a comparative neurological approach and we use a variety of animals, as well as human autopsy material. Light and electron microscopic immunocytochemical techniques and tissue culture, and neuronal labeling methods are widely applied in the laboratory to study cell class specific gene expression.