Shroom Gene Controls Neural Tube Closure

Shroom was originally identified as a mouse mutation that causes exencephaly, acrania, facial clefting, spina bifida, and herniation of internal organs. The shroom gene is expressed in the neuroepithelium, the ventrolateral body wall, and the gut, suggesting that these phenotypes result directly from a loss of shroom protein. Shroom encodes a PDZ domain-containing cytoskeletal protein that can directly bind F-actin and regulate its subcellular distribution in cells.

Investigators at the University of California (Berkeley, USA) employed an amphibian model (the African clawed frog, Xenopus laevis) to study spinal cord closure. They showed that blocking shroom gene activity in normal Xenopus embryos prevented development of rolled neural tubes. On the other hand, shroom protein injected into very early frog embryos, before they would be expected to form a neural tube, caused the as-yet-undifferentiated cells to curl up into a tube. Similarly, shroom protein induced apical constriction of cultured dog kidney cells, which normally never become wedge-shaped. These findings were published in the December 16, 2003, issue of Current Biology.

"These experiments show that, in the embryo, a single protein can bring about this cell shape change, which is staggering, because it implies that this entire bending event can be controlled essentially by controlling a single gene,” explained senior author Dr. John Wallingford, now an assistant professor in the department of molecular, cell and developmental biology at the University of Texas (Austin, USA). "We know this gene is in a really central location, so by identifying things that regulate its expression, and things that function downstream of it, we can get a better picture of the hierarchy and expand the number of genes we know that are involved in neural tube closure. This gives us more candidates to look for in the human condition.”




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