Knockout Mouse Reveals Genetic Mechanism In Defective Mammalian Ear Development

BAR HARBOR -- A control mechanism for the proper development of inner ear "hair cells" -- sensory cells that are critical for normal hearing in mammals such as mice and humans -- has been found to involve two interacting genes in a molecular signaling pathway known to direct cell fate in many different organisms, including fish and insects.

This control mechanism, which involves the genes Jagged2 and Notch1, was identified in a collaborative effort by research teams headed by Dr. Matthew Kelley at the Georgetown University School of Medicine and Dr. Thomas Gridley at The Jackson Laboratory. The results are reported in "The Notch Signaling Pathway Mediates Hair Cell Development in the Mammalian Cochlea" in the March 1999 issue of Nature Genetics.

Dr. Gridley has conducted extensive research on the Notch signaling pathway and led the team that reported last year on developmental defects in Jagged2 knockout mice from The Jackson Laboratory. He describes the pathway -- first studied in the fruit fly -- as a molecular mechanism that mediates communication between cells as they differentiate during embryonic development. In humans, Notch pathway mutations have been implicated in cancer and in several inherited disease syndromes.

"This work clearly establishes that identical mechanisms to control the development of sensory cells operate in both mammals and in lower organisms, such as the fruit fly," said Dr. Gridley. "Such evolutionary conservation of mechanism emphasizes the importance of the Notch signaling pathway for normal development. This pathway is a key regulator controlling the proper development of many different cell types."

The mammalian inner ear, or cochlea, is lined with an intricate "mosaic" of alternating hair cells and non-sensory supporting cells. Normal hearing results when sound waves cause the tiny hairs to oscillate, and the movement is transmitted as electrical impulses through the hair cells to t

Contact: Luther Young
Jackson Laboratory

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