Posts tagged neurodevelopmental disorders
Articles and news from the latest research reports.
Multiple neurodevelopmental disorders have a common molecular cause
Neurodevelopmental disorders such as Down syndrome and autism-spectrum disorder can have profound, lifelong effects on learning and memory, but relatively little is known about the molecular pathways affected by these diseases. A study published by Cell Press October 9th in the American Journal of Human Genetics shows that neurodevelopmental disorders caused by distinct genetic mutations produce similar molecular effects in cells, suggesting that a one-size-fits-all therapeutic approach could be effective for conditions ranging from seizures to attention-deficit hyperactivity disorder.
"Neurodevelopmental disorders are rare, meaning trying to treat them is not efficient," says senior study author Carl Ernst of McGill University. "Once we fully define the major common pathways involved, targeting these pathways for treatment becomes a viable option that can affect the largest number of people."
A large fraction of neurodevelopmental disorders are associated with variation in specific genes, but the genetic factors responsible for these diseases are very complex. For example, whereas common variants in the same gene have been associated with two or more different disorders, mutations in many different genes can lead to similar diseases. As a result, it has not been clear whether genetic mutations that cause neurodevelopmental disorders affect distinct molecular pathways or converge on similar cellular functions.
To address this question, Ernst and his team used human fetal brain cells to study the molecular effects of reducing the activity of genes that are mutated in two distinct autism-spectrum disorders. Changes in transcription factor 4 (TCF4) cause 18q21 deletion syndrome, which is characterized by intellectual disability and psychiatric problems, and mutations in euchromatic histone methyltransferase 1 (EHMT1) cause similar symptoms in a disease known as 9q34 deletion syndrome.
Interfering with the activity of TCF4 or EHMT1 produced similar molecular effects in the cells. Strikingly, both of these genetic modifications resulted in molecular patterns that resemble those of cells that are differentiating, or converting from immature cells to more specialized cells. “Our study suggests that one fundamental cause of disease is that neural stem cells choose to become full brain cells too early,” Ernst says. “This could affect how they incorporate into cellular networks, for example, leading to the clinical symptoms that we see in kids with these diseases.”
(Image: Wellcome Images)
Autism rates steady for two decades
A University of Queensland study has found no evidence of an increase in autism in the past 20 years, countering reports that the rates of autism spectrum disorders (ASDs) are on the rise.
The study, led by Dr Amanda Baxter from UQ’s Queensland Centre for Mental Health Research at the School of Population Health, was a first-of-its-kind analysis of research data from 1990 to 2010.
Dr Baxter said she and her colleagues found that rates had remained steady, despite reports that the prevalence of ASDs was increasing.
“We found that the prevalence of ASDs in 2010 was one in 132 people, which represents no change from 1990,” Dr Baxter said.
“We found that better recognition of the disorders and improved diagnostic criteria explain much of the difference in study findings over time.”
Part of the Global Burden of Disease project, this is the largest study to systematically assess rates and disability caused by ASDs in the community, using data collected from global research findings in the past 20 years.
ASDs are chronic, disabling disorders that stem from problems with brain development.
They affect people from a young age and are among the world’s 20 most disabling childhood conditions.
The study shows that about 52 million children and adults around the globe meet diagnostic criteria for an ASD.
Dr Baxter said researchers hoped the study would help guide health policy and improve support for those with ASD and their families.
“As ASDs cause substantial lifelong health issues, an accurate understanding of the burden of these disorders can inform public health policy as well as help allocate necessary resources for education, housing and employment,” she said.
The study, a collaboration with the University of Leicester and the University of Washington’s Institute for Health Metrics and Evaluation, is published in Psychological Medicine journal.
(Source: uq.edu.au)
Study Links Placental Marker of Prenatal Stress to Brain Mitochondrial Dysfunction
When a woman experiences a stressful event early in pregnancy, the risk of her child developing autism spectrum disorders or schizophrenia increases. Yet how maternal stress is transmitted to the brain of the developing fetus, leading to these problems in neurodevelopment, is poorly understood.
New findings by University of Pennsylvania School of Veterinary Medicine scientists suggest that an enzyme found in the placenta is likely playing an important role. This enzyme, O-linked-N-acetylglucosamine transferase, or OGT, translates maternal stress into a reprogramming signal for the brain before birth.
(Image caption: Mice with reduced OGT in their placenta were shorter and leaner than their normal counterparts.)
“By manipulating this one gene, we were able to recapitulate many aspects of early prenatal stress,” said Tracy L. Bale, senior author on the paper and a professor in the Department of Animal Biology at Penn Vet. “OGT seems to be serving a role as the ‘canary in the coal mine,’ offering a readout of mom’s stress to change the baby’s developing brain.”
Bale also holds an appointment in the Department of Psychiatry in Penn’s Perelman School of Medicine. Her co-author is postdoctoral researcher Christopher L. Howerton. The paper was published online in PNAS this week.
OGT is known to play a role in gene expression through chromatin remodeling, a process that makes some genes more or less available to be converted into proteins. In a study published last year in PNAS, Bale’s lab found that placentas from male mice pups had lower levels of OGT than those from female pups, and placentas from mothers that had been exposed to stress early in gestation had lower overall levels of OGT than placentas from the mothers’ unstressed counterparts.
“People think that the placenta only serves to promote blood flow between a mom and her baby, but that’s really not all it’s doing,” Bale said. “It’s a very dynamic endocrine tissue and it’s sex-specific, and we’ve shown that tampering with it can dramatically affect a baby’s developing brain.”
To elucidate how reduced levels of OGT might be transmitting signals through the placenta to a fetus, Bale and Howerton bred mice that partially or fully lacked OGT in the placenta. They then compared these transgenic mice to animals that had been subjected to mild stressors during early gestation, such as predator odor, unfamiliar objects or unusual noises, during the first week of their pregnancies.
The researchers performed a genome-wide search for genes that were affected by the altered levels of OGT and were also affected by exposure to early prenatal stress using a specific activational histone mark and found a broad swath of common gene expression patterns.
They chose to focus on one particular differentially regulated gene called Hsd17b3, which encodes an enzyme that converts androstenedione, a steroid hormone, to testosterone. The researchers found this gene to be particularly interesting in part because neurodevelopmental disorders such as autism and schizophrenia have strong gender biases, where they either predominantly affect males or present earlier in males.
Placentas associated with male mice pups born to stressed mothers had reduced levels of the enzyme Hsd17b3, and, as a result, had higher levels of androstenedione and lower levels of testosterone than normal mice.
“This could mean that, with early prenatal stress, males have less masculinization,” Bale said. “This is important because autism tends to be thought of as the brain in a hypermasculinized state, and schizophrenia is thought of as a hypomasculinized state. It makes sense that there is something about this process of testosterone synthesis that is being disrupted.”
Furthermore, the mice born to mothers with disrupted OGT looked like the offspring of stressed mothers in other ways. Although they were born at a normal weight, their growth slowed at weaning. Their body weight as adults was 10-20 percent lower than control mice.
Because of the key role that that the hypothalamus plays in controlling growth and many other critical survival functions, the Penn Vet researchers then screened the mouse genome for genes with differential expression in the hypothalamus, comparing normal mice, mice with reduced OGT and mice born to stressed mothers.
They identified several gene sets related to the structure and function of mitochrondria, the powerhouses of cells that are responsible for producing energy. And indeed, when compared by an enzymatic assay that examines mitochondria biogenesis, both the mice born to stressed mothers and mice born to mothers with reduced OGT had dramatically reduced mitochondrial function in their hypothalamus compared to normal mice. These studies were done in collaboration with Narayan Avadhani’s lab at Penn Vet.
Such reduced function could explain why the growth patterns of mice appeared similar until weaning, at which point energy demands go up.
“If you have a really bad furnace you might be okay if temperatures are mild,” Bale said. “But, if it’s very cold, it can’t meet demand. It could be the same for these mice. If you’re in a litter close to your siblings and mom, you don’t need to produce a lot of heat, but once you wean you have an extra demand for producing heat. They’re just not keeping up.”
Bale points out that mitochondrial dysfunction in the brain has been reported in both schizophrenia and autism patients.
In future work, Bale hopes to identify a suite of maternal plasma stress biomarkers that could signal an increased risk of neurodevelopmental disease for the baby.
“With that kind of a signature, we’d have a way to detect at-risk pregnancies and think about ways to intervene much earlier than waiting to look at the term placenta,” she said.
Brain Noise Found to Nurture Synapses
A study has shown that a long-overlooked form of neuron-to-neuron communication called miniature neurotransmission plays an essential role in the development of synapses, the regions where nerve impulses are transmitted and received. The findings, made in fruit flies, raise the possibility that abnormalities in miniature neurotransmission may contribute to neurodevelopmental diseases. The findings, by researchers at Columbia University Medical Center (CUMC), were published today in the online edition of the journal Neuron.
The primary way in which neurons communicate with each another is through “evoked neurotransmission.” This process begins when an electrical signal, or action potential, is transmitted along a long, cable-like extension of the neuron called an axon. Upon reaching the axon’s terminus, the signal triggers the release of chemicals called neurotransmitters across the synapse. Finally, the neurotransmitters bind to and activate receptors of the neuron on the other side of the synapse. Neurotransmitters are packaged together into vesicles, which are released by the hundreds, if not thousands, with each action potential. Evoked neurotransmission was first characterized in the 1950s by Sir Bernard Katz and two other researchers, who were awarded the 1970 Nobel Prize in Physiology or Medicine for their efforts.
“Dr. Katz also found that even without action potentials, lone vesicles are released now and then at the synapse,” said study leader Brian D. McCabe, PhD, assistant professor of pathology and cell biology and of neuroscience in the Motor Neuron Center. “These miniature events — or minis — have been found at every type of synapse that has been studied. However, since minis don’t induce neurons to fire, people assumed they were inconsequential, just background noise.”
Recent cell-culture studies, however, have suggested that minis do have some function and even their own regulatory mechanisms. “This led us to wonder why there would be such complicated mechanisms for regulating something that was just noise,” said Dr. McCabe.
To learn more about minis, the CUMC team devised new genetic tools to selectively up- or down-regulate evoked and miniature neurotransmission in fruit flies (a commonly used model organism for neuronal function and development). This was the first study to identify a unique role for minis in an animal model.
The researchers found that when both types of neurotransmission were blocked, synapse development was abnormal. However, inhibiting or stimulating evoked neurotransmission alone had no effect on synaptic development. “But when we blocked minis, synapses failed to develop,” said Dr. McCabe, “and when we stimulated the release of more minis, synapses got bigger.”
The study also showed that minis regulate synapse development by activating a signaling pathway in neurons involving Trio and Rac1 proteins in presynaptic neurons. These proteins are also found in humans.
It remains to be seen exactly how minis are exerting their effects. “Parallel communication occurs in computer networks,” Dr. McCabe said. “Computers communicate primarily by sending bursts of data bundled into packets. But individual computers also send out pings, or tiny electronic queries, to determine if there is a connection to other computers. Similarly, neurons may be using minis to ping connected neurons, saying in effect, ‘We are connected and I am ready to communicate.’”
The researchers are currently looking into whether minis have a functional role in the mature nervous system. If so, it’s possible that defects in minis could contribute to neurodegenerative disease.
Oxytocin promotes social behavior in infant rhesus monkeys
The hormone oxytocin appears to increase social behaviors in newborn rhesus monkeys, according to a study by researchers at the National Institutes of Health, the University of Parma in Italy, and the University of Massachusetts, Amherst. The findings indicate that oxytocin is a promising candidate for new treatments for developmental disorders affecting social skills and bonding.
Oxytocin, a hormone produced by the pituitary gland, is involved in labor and birth and in the production of breast milk. Studies have shown that oxytocin also plays a role in parental bonding, mating, and in social dynamics. Because of its possible involvement in social encounters, many researchers have suggested that oxytocin might be useful as a treatment for conditions affecting social behaviors, such as autism spectrum disorders. Although oxytocin has been shown to increase certain social behaviors in adults, before the current study it had not been shown to do so in primate infants of any species.
Working with infant rhesus monkeys, the NIH researchers found that oxytocin increased two facial gestures associated with social interactions— one used by the monkeys themselves in certain social situations, the other in imitation of their human caregivers.
“It was important to test whether oxytocin would promote social behaviors in infants in the same respects as it appears to promote social interaction among adults,” said the study’s first author, Elizabeth A. Simpson, Ph.D., postdoctoral fellow of the University of Parma, conducting research in the Comparative Behavioral Genetics Section of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “Our results indicate that oxytocin is a candidate for further studies on treating developmental disorders of social functioning.”
The study was published online in Proceedings of the National Academy of Sciences.
The researchers began by gauging the ability of rhesus macaques to imitate two facial gestures: lip smacking and tongue protrusion. In lip smacking, the lips are protruded and open, then smacked together repeatedly. The study authors wrote that rhesus mothers will engage in this facial gesture with their infants in the first month after giving birth. Tongue protrusion involves a brief protrusion and retraction of the tongue. Although this gesture is seen in other primates and typically not seen in macaques, macaques will imitate it when their human caregivers display it, the study authors added.
By observing the monkeys’ ability to imitate the two gestures, the researchers sought to determine if oxytocin could promote social interaction through a gesture that was natural to them as well as through a gesture not part of their normal communication sequence.
The researchers tested the infants in the first week after birth. Three times a day, every other day, the caregivers would demonstrate the facial gestures in sequence to the infant monkeys, while the animals’ responses were recorded on video. At this phase of the study, the researchers found that some of the monkeys mimicked their caregivers’ gestures more frequently than did other monkeys. The researchers referred to the monkeys who gestured more frequently as strong imitators.
Beginning in the second week of life, the researchers tested the monkeys on two separate days. The infant monkeys inhaled an aerosolized dose of oxytocin in one session, and a dose of saline in the other. In each session, the dose was delivered through an inhalation mask held gently over the animal’s face.
Overall, the monkeys were more communicative after receiving oxytocin, more frequently making facial gestures, than they were after receiving the saline. The monkeys were more likely to engage in lip smacking than tongue protrusion, but were more likely still to engage in either of these gestures after oxytocin than after the saline. There also were differences in the frequency of gesturing among the individual monkeys, with the strong imitators becoming even stronger imitators after receiving oxytocin.
After oxytocin exposure, the strong imitators were more likely to look at caregivers and stand close to them than they were after the saline. Looking into a caregiver’s face and remaining in close proximity to a caregiver are indicators of social interaction and social interest, Dr. Simpson said.
In another test, the researchers found that after exposure to oxytocin, monkeys had lower levels of cortisol in their saliva. Cortisol is produced by the adrenal glands in response to stress. Lower cortisol levels after oxytocin exposure indicate that oxytocin may also function to diminish anxiety, the researchers wrote.
Cognitive scientists use ‘I spy’ to show spoken language helps direct children’s eyes
In a new study, Indiana University cognitive scientists Catarina Vales and Linda Smith demonstrate that children spot objects more quickly when prompted by words than if they are only prompted by images.
Language, the study suggests, is transformative: More so than images, spoken language taps into children’s cognitive system, enhancing their ability to learn and to navigate cluttered environments. As such the study, published last week in the journal Developmental Science, opens up new avenues for research into the way language might shape the course of developmental disabilities such as ADHD, difficulties with school, and other attention-related problems.
In the experiment, children played a series of “I spy” games, widely used to study attention and memory in adults. Asked to look for one image in a crowded scene on a computer screen, the children were shown a picture of the object they needed to find — a bed, for example, hidden in a group of couches.
"If the name of the target object was also said, the children were much faster at finding it and less distracted by the other objects in the scene," said Vales, a graduate student in the Department of Psychological and Brain Sciences.
"What we’ve shown is that in 3-year-old children, words activate memories that then rapidly deploy attention and lead children to find the relevant object in a cluttered array," said Smith, Chancellor’s Professor in the Department of Psychological and Brain Sciences. "Words call up an idea that is more robust than an image and to which we more rapidly respond. Words have a way of calling up what you know that filters the environment for you.”
The study, she said , “is the first clear demonstration of the impact of words on the way children navigate the visual world and is a first step toward understanding the way language influences visual attention, raising new testable hypotheses about the process.”
Vales said the use of language can change how people inspect the world around them.
"We also know that language will change the way people perform in a lot of different laboratory tasks," she said. "And if you have a child with ADHD who has a hard time focusing, one of the things parents are told to do is to use words to walk the child through what she needs to do. So there is this notion that words change cognition. The question is ‘how?’"
Vales said their research results “begin to tell us precisely how words help, the kinds of cognitive processes words tap into to change how children behave. For instance, the difference between search times, with and without naming the target object, indicate a key role for a kind of brief visual memory known as working memory, that helps us remember what we just saw as we look to something new. Words put ideas in working memory faster than images.”
For this reason, language may play an important role in a number of developmental disabilities.
"Limitations in working memory have been implicated in almost every developmental disability, especially those concerned with language, reading and negative outcomes in school," Smith said. "These results also suggest the culprit for these difficulties may be language in addition to working memory.
"This study changes the causal arrow a little bit. People have thought that children have difficulty with language because they don’t have enough working memory to learn language. This turns it around because it suggests that language may also make working memory more effective."
How does this matter to child development?
"Children learn in the real world, and the real world is a cluttered place," Smith said. "If you don’t know where to look, chances are you don’t learn anything. The words you know are a driving force behind attention. People have not thought about it as important or pervasive, but once children acquire language, it changes everything about their cognitive system."
"Our results suggest that language has huge effects, not just on talking, but on attention — which can determine how children learn, how much they learn and how well they learn," Vales said.
A Critical Window into the Developing Human Brain Profiled in Nature
First major report using data from the BrainSpan Atlas of the Developing Human Brain shines a light on where genes are turned on in the brain during mid-pregnancy, what goes wrong in developmental disorders like autism, and what makes human brains unique.
Researchers at the Allen Institute for Brain Science have generated a high-resolution blueprint for how to build a human brain, with a detailed map of where different genes are turned on and off during mid-pregnancy at unprecedented anatomical resolution. This first major report using data from the BrainSpan Atlas of the Developing Human Brain is published in the journal Nature this week. The data provide exceptional insight into diseases like autism that are linked to early brain development, and to the origins of human uniqueness. The rich data set is publicly available to everyone via the Allen Brain Atlas data portal.
“Knowing where a gene is expressed in the brain can provide powerful clues about what its role is,” says Ed Lein, Investigator at the Allen Institute for Brain Science. “This atlas gives a comprehensive view of which genes are on and off in which specific nuclei and cell types while the brain is developing during pregnancy. This means that we have a blueprint for human development: an understanding of the crucial pieces necessary for the brain to form in a normal, healthy way, and a powerful way to investigate what goes wrong in disease.”
This paper represents the first major report to make use of data collected for the BrainSpan Atlas of the Developing Human Brain, a big science consortium initiative which seeks to create a map of the transcriptome across the entire course of human development. “Coming on the first anniversary of the BRAIN Initiative, this is a terrific example of the potential for public-private partnerships to accelerate progress in neuroscience,” says Lein.
Thomas R. Insel, Director of the National Institute of Mental Health, praises the BrainSpan Atlas as an already invaluable tool to researchers. “While we have had previous reports of molecular and cellular changes during human brain growth, the BrainSpan Atlas is the first comprehensive map of the dramatic trajectory of gene expression across prenatal and postnatal development,” he says. “This atlas is already transforming the way scientists approach human brain development and neurodevelopmental disorders like autism and schizophrenia. Although the many genes associated with autism and schizophrenia don’t show a clear relationship to each other in the adult brain, the BrainSpan Atlas reveals how these diverse genes are connected in the prenatal brain.”
(Source: alleninstitute.org)
Brain Damage in Children—The Result of Too Many Chemicals?
A new report is sounding the alarm of a “silent epidemic” of childhood neurological disorders linked to neurotoxic compounds.
While genetics is known to play a role in neurological problems, only 30 to 40 percent of neurodevelopmental disorders can be definitively tied to family history. “There are a lot of chemicals out there that have been shown to have the capability to injure the developing brain,” says study coauthor Philip Landrigan, MD, professor and chair of the department of community and preventive medicine at Mount Sinai School of Medicine in New York City and one of the world’s foremost authorities on children’s environmental health. “And we’re very concerned that a number of chemicals in everyday products have never been properly tested to determine whether they’re toxic to the human brain.”
In the new report, Dr. Landrigan and his coauthor identified six chemicals that have been discovered, within the past seven years, to trigger brain damage in children. In 2006, he and other researchers ID’d lead, methylmercury, arsenic, polychlorinated biphenyls (PCBs), and toluene as known contributors to rising rates of neurodevelopmental disorders like autism, attention-deficit hyperactivity disorder, and learning disabilities.
In many people with autism and other neurodevelopmental disorders, different parts of the brain don’t talk to each other very well. Scientists have now identified, for the first time, a way in which this decreased functional connectivity can come about. In a study published online today in Nature Neuroscience, scientists at the European Molecular Biology Laboratory (EMBL) in Monterotondo, Italy, and collaborators at the Istituto Italiano di Tecnologia (IIT), in Rovereto, and La Sapienza University in Rome, demonstrate that it can be caused by cells called microglia failing to trim connections between neurons.
“We show that a deficit in microglia during development can have widespread and long-lasting effects on brain wiring and behaviour,” says Cornelius Gross, who led the study. “It leads to weak brain connectivity, decreased social behaviour, and increased repetitive behaviour, all hallmarks of autism.”
The findings indicate that, by trimming surplus connections in the developing brain, microglia allow the remaining links to grow stronger, like high-speed fibre-optic cables carrying strong signals between brain regions. But if these cells fail to do their job at that crucial stage of development, those brain regions are left with a weaker communication network, which in turn has lifelong effects on behaviour.
Yang Zhan, a postdoctoral fellow in Gross’ lab at EMBL, analysed the strength of connections between different areas of brain in mice that were genetically engineered to have fewer microglia during development. Working with Alessandro Gozzi’s lab at IIT and Davide Ragozzino at La Sapienza University, the EMBL scientists combined this approach with high-resolution fMRI (functional Magnetic Resonance Imaging) scans of the mice’s brains, taking full advantage of a novel technique developed at IIT, which enables scientists to obtain detailed, three-dimensional maps of the brain’s functional connections. The team found that mice with fewer microglia had weaker connections between neurons, and less cross-talk between different brain regions. When Rosa Paolicelli, a PhD student in Gross’ lab, studied the mice’s behaviour, she discovered that mice with fewer microglia and decreased connectivity displayed behaviours commonly associated with autism spectrum disorders. These mice spent more time repeatedly grooming themselves, and avoided social interactions.
“This is an exciting time to be studying microglia,” Gross concludes: “they’re turning out to be major players in how our brain gets wired up.”
Impaired cell division leads to neuronal disorder
Prof. Erich Nigg and his research group at the Biozentrum of the University of Basel have discovered an amino acid signal essential for error-free cell division. This signal regulates the number of centrosomes in the cell, and its absence results in the development of pathologically altered cells. Remarkably, such altered cells are found in people with a neurodevelopmental disorder, called autosomal recessive primary microcephaly. The results of these investigations have been published in the current issue of the US journal “Current Biology”.
Cell division is the basis of all life. Of central importance is the error-free segregation of genetic material, the chromosomes. A flawless division process is a prerequisite for the development of healthy, new cells, whilst errors in cell division can cause illnesses such as cancer. The centrosome, a tiny cell organelle, plays a decisive role in this process.
Prof. Erich Nigg’s research group at the Biozentrum of the University of Basel has investigated an important step in cell division: the duplication of the centrosome and its role in the correct segregation of the chromosomes into two daughter cells. The protein STIL has an essential function in this process. It ensures that centrosome duplicate before one half of the genetic material is transported into each of the two daughter cells.
KEN-Box important for protein breakdown
During cell division, the protein STIL is degraded. If this does not occur, the protein accumulates in the cell, which then causes an overproduction of centrosomes. As a consequence, mis-segregated chromosomes are incorporated into the daughter cells, which then represent cells with faulty genetic material. The scientists discovered an amino acid signal on the STIL protein, a so-called KEN-Box, and showed that this is critical for the breakdown of the protein: “The Ken-Box is the signal that orders the protein degradation machinery to break down the STIL protein,” explains Christian Arquint, the first author of this publication. In the absence of the KEN-Box, the protein is not degraded.
Absence of the KEN-Box causes microcephaly
In some patients with microcephaly, a neuronal disorder that leads to a reduced number of nerve cells being produced and, therefore, a smaller brain, the KEN-box is lacking from the STIL protein. The scientists were thus able to demonstrate a tantalizing connection between the absence of this particular amino acid signal and an illness. “When during our investigations of cell division and centrosome duplication we came across a connection to the disorder microcephaly, we were particularly pleased, as this helps us to better understand how this disorder develops“, says Christian Arquint.
In the future, the research group led by Erich Nigg plans to uncover other connections between errors of cell division and the illness microcephaly. They also want to focus on the investigation of other proteins that play important roles in the process of cell division, in particular those involved in centrosome duplication.