Researchers from the Hebrew University of Jerusalem and the Universidade NOVA de Lisboa have identified a molecular pathway that may explain how folic acid (vitamin B9) helps prevent neural tube defects, linking the vitamin to a key developmental signal made from vitamin A.
Folic acid supplementation during pregnancy is the commonly accepted treatment to prevent neural tube defects.
“Before an embryo has a recognizable brain or spinal cord, a sheet of cells called the neural plate begins to fold upward,” said Hebrew University of Jerusalem Ph.D. student Tamir Edri and colleagues.
“Its edges must meet and close, almost like a zipper, to make the neural tube. If that process goes wrong, neural tube defects can result.”
“Scientists have long known that folic acid can help prevent many of these defects. But the vitamin seems to be doing more than simply supplying nutrients.”
In the new study, the authors found that folic acid helps switch on ALDH1L1, a gene that makes the ALDH1L1 enzyme.
“The ALDH1L1 enzyme can then help turn a vitamin A-related molecule called retinaldehyde into retinoic acid,” they said.
“Retinoic acid acts like a set of instructions, telling developing cells when to grow, what to become, where to go, and when to stop dividing.”
To test whether ALDH1L1 was truly important, the researchers used frog embryos, a common model for studying early development.
They created embryos with neural tube closure problems and then treated them with folic acid, which helped many of the embryos develop more normally.
Then the scientists disrupted the ALDH1L1 gene. This time, folic acid lost its protective effect.
The result was a major clue: without ALDH1L1, folic acid could no longer rescue the developing neural tube.
The authors pushed the idea further, demonstrating that the human ALDH1L1 can produce retinoic acid.
They also found evidence that the same biological pathway is active in mammalian cells, strengthening the possibility that the mechanism could be relevant to humans.
Edri and co-authors also saw what happened when this signaling system broke down.
