Researchers from the Hebrew University of Jerusalem and NOVA de Lisboa University have uncovered a molecular pathway that elucidates how folic acid (vitamin B9) plays a role in preventing neural tube defects by connecting it to essential developmental signals derived from vitamin A.
Folic acid supplementation during pregnancy is a commonly accepted treatment to prevent neural tube defects.
“Before the fetus forms a recognizable brain or spinal cord, a sheet of cells called the neural plate begins to fold upward,” said Dr. student Tamir Edri and his colleagues.
“To create a neural tube, its ends have to connect and close, almost like a zipper. If that process fails, a neural tube defect can occur.”
“Scientists have long known that folic acid can help prevent many of these defects. But it appears the vitamin does more than just provide nutrients.”
In a new study, the authors found that folic acid helps turn on the switch. ALDH1L1the gene that makes the ALDH1L1 enzyme.
“The ALDH1L1 enzyme may help convert a vitamin A-related molecule called retinaldehyde to retinoic acid,” the researchers said.
“Retinoic acid acts like a set of instructions for developing cells, telling them when to grow, what to become, where to go, and when to stop dividing.”
To test whether ALDH1L1 is really important, the researchers used frog embryos, a common model for studying early development.
They created embryos with neural tube closure problems and treated them with folic acid, which helped many develop more normally.
Then scientists disrupted this world. ALDH1L1 gene. This time, folic acid has lost its protective effect.
The results were a big clue. Without ALDH1L1, folic acid would be unable to rescue the developing neural tube.
The authors took this idea further and demonstrated that human ALDH1L1 can produce retinoic acid.
They also found evidence that the same biological pathway is active in mammalian cells, strengthening the possibility that this mechanism is relevant in humans.
Edri and his coauthors also looked at what happened when this signaling system failed.
“When retinoic acid levels are too low, the cells that become part of the nervous system grow too quickly. The neural plate has enlarged abnormally. Folic acid helped restore cell growth to normal, but only if…” ALDH1L1 I was working,” they said.
The findings also raised another possibility. ALDH1L1 uses molecules derived from vitamin A to produce retinoic acid, so the researchers tested whether vitamin A and folic acid work together.
In their fetal experiments, small amounts of retinol, a form of vitamin A, improved the effects of low doses of folic acid.
This does not mean that pregnant women should start taking additional vitamin A.
Scientists warn that too much vitamin A can itself cause severe birth defects, and that healthy development depends on keeping retinoic acid levels within a narrow range.
“Rather, this discovery gives us a new way to think about a decades-old question,” they said.
“Folic acid, acting alone, may not protect the developing nervous system.”
“This may work in part by helping the embryo produce the right amount of another important developmental signal at the precise time.”
“This finding may also help explain why folic acid, while effective in many pregnancies, does not prevent all neural tube defects.”
“An issue with the ALDH1L1-retinoic acid pathway may be one possible reason, but more research is needed to determine whether the same mechanism operates in human pregnancy.”
team’s paper On July 30, 2026, Proceedings of the National Academy of Sciences.
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Tamir Edri others. 2026. Prevention of neural tube defects by folic acid requires retinoic acid produced by ALDH1L1. PNAS 123 (31): e2616501123;doi: 10.1073/pnas.2616501123
Source: www.sci.news
