Development, maturation and function of the auditory and somatosensory systems.
Disorders of sensation are inherent to a variety of inherited and acquired human diseases. Our goal is to understand the molecular signals that control sensory system development and how derangements of development affect animal behavior. In this way, we hope to gain insight into the pathogenesis of a broad range of human diseases and to discover novel therapeutic strategies to treat them.
Central deafness. Hearing loss affects approximately 15% of the US population and often leads to difficulties with communication and decreased quality of life. Great strides have been made toward understanding the pathogenesis of hearing loss associated with disorders of the ear. However, hearing loss arising from disruptions or developmental perturbations of the central nervous system is poorly understood.
This project examines the development of multiple components of the central auditory system. The ultimate goals are to understand where these structures arise, the developmental relationships of the neurons in these structures, and how perturbations of one part of the system effect the development and function of other components. To accomplish these goals, we use conditional knockout strategies in mice to disrupt gene expression in both space and time. This approach led us to the creation of the first mouse models of central deafness and has uncovered interesting relationships between the peripheral and central auditory pathways. We are now in the process of characterizing the effects of central neuronal loss on the ear and identifying genes that direct the specification and development of auditory neurons in different regions of the brainstem. We use a combination of behavioral, electrophysiological, histological and molecular biological techniques to determine how various disruptions affect both structure and function.
Touch sensation. The cutaneous somatosensory system detects mechanical stimuli interpreted by the brain as the sense of touch. Defects in the central and peripheral components of this system occur in a number of human diseases including injury, stroke, and neurobehavioral disorders.
Four main classes of sensory receptors in mammalian skin mediate different aspects of the sense of touch. One of these specialized structures, the Merkel cell-neurite complex, is thought to be important for two-point discrimination and the detection of texture, shape and curvature. These receptors consist of Merkel cells, a distinct cell population found at the epidermal/dermal border, and the afferent somatosensory fibers that innervate them. Merkel cell-neurite complexes are found in touch-sensitive areas of the skin including whisker follicles, glabrous (hair-less) skin surfaces such as the hands and feet, and specialized epithelial structures in the hairy skin called touch domes.
This project studies the development of Merkel cell-neurite complexes with the goals of understanding where they come from and what they do. We use a variety of behavioral tests to study the effects of Merkel cell loss on mouse behavior, and we are exploring the genetic pathways that control the development of these cells and the neurons that innervate them.
Chonko, K.T., Jahan, I., Stone, J., Wright, M.C., Fujiyama, T., Hoshino, M., Fritzsch, B. and Maricich, S.M. Atoh1 directs hair cell differentiation and survival in the late embryonic mouse inner ear. Dev Biol, in press. (2013).
Maricich, S.M., Cameron, K.M., Mathes E.L. and Brewer, B.M. Rodents rely upon Merkel cells for texture discrimination tasks. J Neurosci, 32(10): 3296-3300, 2012.
Xia, A., Gao, S.S., Yuan, T., Osborn, A., Bress, A., Pfister, M., Maricich, S.M., Pereira, F.A. and Oghalai, J.S. Deficient forward transduction and enhanced reverse transduction in the alpha tectorin C1509G human hearing loss mutation. Dis Model Mech, 3(3-4): 209-223, 2010.
Morrison, K.M., Miesegaes, G.R., Lumpkin, E.A. and Maricich, S.M. Mammalian Merkel cells are descended from the epidermal lineage. Dev Biol, 336(1): 76-83, 2009.
Maricich, S.M., Xia, A., Wang, V.Y., Oghalai, J.S., Fritzsch, B. and Zoghbi, H.Y. Atoh1 lineal neurons in the cochlear nucleus are required for hearing and for the survival of brainstem accessory auditory and spiral ganglion neurons. J Neurosci, 29(36): 11123-11133, 2009.
Maricich, S.M., Wellnitz, S.A., Nelson, A.M., Lesniak, D.R., Gerling G.J., Lumpkin, E.A. and Zoghbi, H.Y. Merkel cells are essential for light touch responses. Science, 324: 1580-1582, 2009.