In some genetic cases of microcephaly, stem cells fail to launch

August 24, 2016
From top to bottom: normal, NDE1 mutant, NDEL1 mutant, and NDE1 + NDEL1 double mutant cells. Each panel represents 30-minute intervals. Credit: Columbia University Medical Center

In a very severe, genetic form of microcephaly, stem cells in the brain fail to divide, according to a new Columbia University Medical Center study that may provide important clues to understanding how the Zika virus affects the developing brain.

The study was published August 24 in Nature Communications.

Due to the Zika virus, the world is suffering from its first known epidemic of microcephaly, a devastating brain developmental condition that substantially reduces the number of neurons in the brain, along with brain size and function at birth.

Mutations in a number of human genes have been implicated in causing the relatively rare occurrence of this disease. Mutations in one such gene - NDE1 (referred to as "nood-E") - cause a particularly severe form of microcephaly. The Columbia researchers—David Doobin, an MD/PhD student, Richard Vallee, PhD, professor of pathology and cell biology, and others in Dr. Vallee's lab—reasoned that investigating NDE1's role in microcephaly should provide important clues to the causes of microcephaly in general.

In the study, the researchers found that interfering with NDE1 expression severely inhibited the proliferation of in the developing rat brain. These stem cells, known as radial glial progenitors (RGPs), undergo rapid repeated divisions over the weeks-to-months-long process of brain development.

Other genes that cause microcephaly are known to impair RGP proliferation, usually by interrupting the cells when they are in the midst of dividing.

The new study found that NDE1 defects can stop RGPs before division even begins at three distinct arrest points. The net result is a complete failure of these cells to divide, explaining the severity of the NDE1-associated microcephaly.

Numerous labs are investigating the effects of Zika on the , and some studies already suggest that the virus targets RGP cells in the developing brain. Dr. Vallee's lab, along with that of Vincent Racaniello, PhD and Amy Rosenfield, PhD, in Columbia's Department of Microbiology, plan to test for similarities in the damage to neuronal stem cells caused by Zika vs. NDE1 mutations.

Explore further: Microcephaly discoveries made in non-Zika cases help explain abnormal brain growth

More information: Severe NDE1-Mediated Microcephaly Results from Neural Progenitor Cell Cycle Arrests at Multiple Specific Stages, Nature Communications, 2016.

Related Stories

Microcephaly discoveries made in non-Zika cases help explain abnormal brain growth

August 5, 2016
Long before Zika virus made it a household word, the birth defect called microcephaly puzzled scientists and doctors—even as it changed the lives of the babies born with it during the pre-Zika era.

Five new confirmed microcephaly cases in Colombia may be harbingers of epidemic

June 28, 2016
Just when it seemed that missing cases of microcephaly in Colombia were straining the credibility of the Zika virus' connection to the birth defects, the latest report from Colombia includes five new cases of microcephaly ...

Two Zika proteins responsible for microcephaly identified

August 11, 2016
USC researchers have tracked down two Zika proteins potentially responsible for thousands of microcephaly cases in Brazil and elsewhere—taking one small step toward preventing Zika-infected mothers from birthing babies ...

Why neural stem cells may be vulnerable to Zika infection

March 30, 2016
Zika's hypothesized attraction to human neural stem cells may come from its ability to hijack a protein found on the surface of these cells, using it as an entryway to infection. In Cell Stem Cell on March 30, researchers ...

Study provides details of possible link between Zika and severe joint condition at birth

August 9, 2016
A study published by The BMJ today provides more details of an association between Zika virus infection in the womb and a condition known as arthrogryposis, which causes joint deformities at birth, particularly in the arms ...

Panama finds first case of microcephaly tied to Zika

March 19, 2016
Doctors in Panama have identified a baby born with a rare brain disorder thought to be linked to Zika, the first such case outside Brazil.

Recommended for you

Make way for hemoglobin

August 18, 2017
Every cell in the body, whether skin or muscle or brain, starts out as a generic cell that acquires its unique characteristics after undergoing a process of specialization. Nowhere is this process more dramatic than it is ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

New technique overcomes genetic cause of infertility

August 17, 2017
Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

Inhibiting a protein found to reduce progression of Alzheimer's and ALS in mice

August 17, 2017
(Medical Xpress)—A team of researchers with Genetech Inc. and universities in Hamburg and San Francisco has found that inhibiting the creation of a protein leads to a reduction in the progression of Alzheimer's disease ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.