University of Oregon researchers using Drosophila have identified a steroid hormone that creates a vital transition in early brain development in which neural originate cells properly change gears to produce different kinds of neurons.
Their discovery — a fundamental progress for biology and neuroscience, and detailed in a papers published April 10 in the journal eLife — also may shed new light upon maternal hypothyroidism, a human condition in which too little thyroid is produced and is dangerous for pregnant women and their particular developing babies.
In their paper, the UO team, which also included Brandon Mark, a graduate student in biology, tied the hormone ecdysone to some previously unknown sequence of gene expression in Drosophila stem cells. The body hormone in the fruit fly is essentially the equivalent of the human thyroid body hormone, said the study’s lead author Mubarak Hussain Syed, a postdoctoral researcher in the lab of co-author Philip Doe.
“Our finding is the first sort of hormones regulating time-sensitive gene transitions during neurogenesis, plus it offers exciting insights into how problems with hormone signaling could be implicated in neurological diseases, ” Syed mentioned. “During gestation, the deficiency of thyroid hormone can result in serious neurological defects, mental retardation and irreversible fetal human brain damage. ”
Normal thyroid production that individuals controls food metabolism, which, in turn, regulates body temperature plus heart rhythm. When thyroid levels are too low, women that are pregnant are at risk for miscarriage, hypertension and premature delivery.
A fetus requires thyroid from the mom during the first 12 weeks of pregnancy, after which the fetus can produce its own. Babies born to mothers along with undiagnosed or untreated hypothyroidism are at risk for bad brain development and learning disabilities.
Within fruit fly larvae used in the study, the action from the hormone depended on the timely appearance of its receptor, which usually appears midway through larval life in neural come cells. This is a vital stage where changes in gene expression are necessary to control the number and identity of different neurons required to complete brain formation.
“Fruit lures allow us to study brain development in a simpler patient with a shorter life cycle and a more accessible human brain, yet one that shares a great deal of genetic information with human beings, said Syed, who is based in the UO Institute associated with Neuroscience and Institute of Molecular Biology, where he works together with Doe.
Doe, who also is a Howard Hughes Medical Institute investigator based at the UO, had been elected May 2 into the National Academy of Sciences in recognition of his work in cell development, which includes neural stem cells and the development of the central nervous system within fruit flies.
Neural stem cells separate to give rise to all of the different cell types within the brain. How they do so is a mystery on which Doe offers spent years studying. Previous work in his lab has demonstrated that stem cells can express different genes with time to change the identity the neurons that they make.
Human brain development begins during the third week associated with gestation, when a group of stem cells known as neural originate cells are allocated to make the entire brain.
“Human brain development requires similar transitions in the kind of neurons made by neural stem cells during fetal growth, ” Doe said. “Failure to make the full, diverse enhance of neurons would be catastrophic for brain development. inch
Such failure to transition gene appearance can lead to a proliferation of cells that produce cancers.
“Fruit fly neural stem cells can divide over time to make more and more different kinds of brain cells, inch Syed said. “An interesting and important question is just how are all of these different kinds of brain cells generated? How does the neural stem cells know when to stop making these types of neurons? ”
Using fruit fly larvae, the UO team sought to determine the sequence of gene expression and the mechanism by which the neural stem tissues switch from expressing one gene to expressing the following. Doing so helps to also understand how neural stem cells understand when to stop dividing.
By blocking junk signaling in neural stem cells in the experiments, Syed’s team was able to show the hormone’s importance.
“By identifying a cellular mechanism by which hormone signaling regulates brain development, we come closer to understanding how these types of processes contribute to neurodevelopmental and neurodegenerative diseases, ” Syed said.