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Events coordination during embryogenesis
Date:10/29/2013

on early in development, Brachyury binds the CRMs at multiple binding sites. However, genes that are expressed later in notochord development are controlled by Brachyury through single binding sites, while the notochord genes with the latest onsets are controlled by Brachyury indirectly, through a relay mechanism that involves other transcription factors. The paper shows an example of the effects of a mutation in the CRM that controls notochord expression of a laminin gene. In sea squirts as well as in humans, laminins are major components of the basement membranes and extracellular matrix that hold cells together within tissues, and are key regulators of cell migration, cell adhesion and cell proliferation. The Ciona laminin notochord CRM, which was identified in the Di Gregorio lab, requires two cooperative binding sites for Brachyury. When either one of these sites is mutated, Brachyury is unable to bind to that site, but can still bind to the remaining one.

"As a consequence, the CRM is still active in the notochord, but the full onset of its activity is delayed by a few hours, which is a crucial interval during the development of an organism," says Dr. Yutaka Nibu, adjunct assistant research professor and co-senior author of the study. "Such delay could cause a birth defect by slowing down the synthesis of a building block necessary for the organism to form properly, or might postpone the activation of a tumor suppressor gene and trigger cancer formation."

"Imagine that the gene is the light in a specific room of your house, and that the room is a specific cell in your body," adds Dr. Di Gregorio, an associate professor. "To turn the light on, you need to flip the light switch the CRM. A mutation that inactivates your switch would keep your room in the dark. However, a mutation that delays the onset of activity of your switch would still let you turn on the light, but only at a later time. If you had to perform any task in that room that req
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Events coordination during embryogenesis
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