BBS Faculty Member - Lisa Goodrich

Lisa Goodrich

Department of Neurobiology

Harvard Medical School
Goldenson Building, Room 442
220 Longwood Avenue
Boston, MA 02115
Tel: 617-432-2951
Fax: 617-432-2949
Email: lisa_goodrich@hms.harvard.edu
Visit my lab page here.



We are investigating the molecular interactions that guide the development of the nervous system. We are particularly interested in how generic developmental mechanisms are able to create the highly specialized neural circuits that underlie our ability to perceive and interact with the world. We study this question in two complementary sensory systems: the inner ear and the eye. In the auditory system, a relatively homogeneous population of sensory ganglion neurons faithfully transmits sound information from hair cells in the cochlea to target neurons in the auditory brainstem. We are analyzing the transcriptional networks that ensure that these neurons acquire the characteristics required for the perception of sound, with the long term goal of recreating these events in stem cells. In parallel, we are studying how another type of neurons, the amacrine cells of the retina, develop their own unique features and how these properties impact the wiring of the eye. Remarkably, we have found that even subtle changes in amacrine cell morphology can induce a major rearrangement of retinal circuits.

Our work on circuit assembly is paired with studies on the development of an organ with a highly intricate three-dimensional morphology, the inner ear. The inner ear houses three semicircular canals that are oriented with the three dimensions of space, as well as a coiled cochlea that extends ventrally. Even small changes in the size, shape, or arrangement of these structures can prevent normal hearing and balance. The complex shape of the mature inner ear is sculpted from an initially simple sphere of epithelium. We discovered that the poorly characterized Lrig proteins, which belong to the Ig superfamily, control this process in part by controlling expression of the axon guidance molecule Netrin. Current efforts are aimed at revealing molecular functions for the Lrig proteins and at dissecting the unexpected role of Netrin in this system.

We employ a wide variety of techniques to analyze the molecular properties of individual proteins and then link these properties back to the whole animal. We define transcriptional networks using microarrays, deep sequencing, and ChiP assays and dissect signaling pathways using biochemical approaches such as yeast two hybrid screens and mass spectrometry. Rapid tests for protein function are performed using in vitro assays and electroporations. Taking advantage of the growing repertoire of tools for studying the mouse nervous system, we are able to visualize and manipulate neural networks, including live imaging of neurons in the developing cochlea and a Cre-dependent RNAi approach for discovering new circuit assembly genes. Since defects in hearing are easily detected using behavioral and electrophysiological assays, we are ultimately able to correlate cellular defects with changes in auditory function.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 


 

Deans, M.R., Abraira, V.E., Tucker, A.F., and L.V. Goodrich (2011) Control of neuronal morphology by the atypical cadherin Fat3. Neuron, 71(5):820-32.

Lu, C.C., Appler, J.M., Houseman E.A., and L.V. Goodrich (2011) Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly.
J. Neuroscience, 31(30):10903-18.

Appler, J.M. and L.V. Goodrich (2011) Connecting the ear to the brain: molecular mechanisms of auditory circuit assembly.
Progress in Neurobiology, 93(4): 488-508.

Abraira, V.E., Satoh, T., Fekete, D.M., and L.V. Goodrich (2010) Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis.
PLoS One, 5(2):e8981.

Abraira, V.E., Del Rio, T., Tucker, A.F., Slonimsky, J., Keirnes, H.L., and L.V. Goodrich. (2008) Cross-repressive interactions between Lrig3 and Netrin1 shape the architecture of the inner ear.
Development, 135(24):4091-9.

Koundakjian, E.J., Appler, J.L., and L.V. Goodrich (2007) Auditory neurons make stereotyped wiring decisions before maturation of their targets.
J. Neuroscience, 27(51):14078-88.



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