Mechanism Discovered For Determining Early Vertebrate Body Plan: New Zebrafish Mutants Afford Deeper Look Into Embryonic Patterning

hree mutants -- swirl, somitabun and snailhouse -- which are critical in determining abdominal regions of the embryo. Mullins and lead authors Vu H. Nguyen and Bettina Schmid, both of whom are doctoral students in Mullins' lab, postulate that the growth of the neural crest -- a neural tissue found at the back-belly boundary in normal embryos -- is determined by a gradient of bmp activity from the back to the front of the embryo. This activity is modulated by other proteins produced in the abdominal region that differentially repress bmp and subsequently effect its actions on the three genes. This modulating gradient is what sets up the normal patterning of neural tissue growth in the back region of the embryo and other tissue types in the abdominal region.

"In the swirl mutant, all abdominal tissue is absent, but the surprise came when we started to look at the dorsal neural tissue and found that most of it expanded and took over the ventral side," says Mullins. "The swirl embryos contain rings of hind brain tissue growing around the circumference instead of just running down the back. The embryos have spiraled neural tissue--hence the mutants' names." Interestingly, the somitabun mutant (named after a popular swirled cinnamon pastry) shows an expanded growth of the neural crest, whereas in the swirl mutant it's absent. The swirl and somitabun genes have a strong, but opposite, effect on the development of the neural crest, whereas snailhouse plays a smaller role.

Previous work postulated that the neural crest was specified later in development. The Mullins team found that this important event happens much earlier, about five hours earlier in the development of zebrafish. Time-wise, this corresponds in mammals to a day to a couple of days earlier, a stage sometimes crucial to catching a rare glimpse of the earliest stages of vertebrate development.

This work is described in a July issue of Developmental Biology and funded by the

Contact: Karen Young Kreeger
University of Pennsylvania School of Medicine

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