Breaking News
November 16, 2018 - Researchers find no link between ‘allergy friendly’ dogs and lower risk of asthma
November 16, 2018 - Researchers elucidate new rules of connectivity of neurons in the neocortex
November 16, 2018 - Treating children with ‘bubble baby disease’
November 16, 2018 - AHA: PTSD Common Among Those Who Suffer Tear in the Aorta’s Wall
November 16, 2018 - Many RA patients’ pain related to central nervous system
November 16, 2018 - Changes in Himalayan gut microbiomes linked to diet
November 16, 2018 - Inhibition of prostaglandin E2 enhances ability to combat infectious colitis
November 16, 2018 - Chronic dry eye can slow reading rate and disrupt day to day tasks
November 16, 2018 - Researchers develop new drug molecule that inhibits inflammation
November 16, 2018 - Dementia symptoms peak in winter and spring, study finds
November 16, 2018 - Stanford tobacco researcher weighs in on JUUL
November 16, 2018 - Increasing omega-3 fatty acid intake during pregnancy reduces risk of premature birth, review finds
November 16, 2018 - Researchers find no link between infants waking up at night and later developmental problems
November 16, 2018 - Both parents and children agree about confidential medical services
November 16, 2018 - FDA warns against use of unapproved pain medications with implanted pumps
November 16, 2018 - Precision medicine-based approach to slow or reverse biologic drivers of Alzheimer’s disease
November 16, 2018 - Study provides new insight into norovirus outbreaks, may help guide efforts to develop vaccines
November 16, 2018 - Inexpensive, portable air purifier could help protect the heart from pollution
November 16, 2018 - New 15-minute scan could help diagnose brain damage in babies up to two years old
November 16, 2018 - Deep brain stimulation not effective for treating early Alzheimer’s
November 16, 2018 - Traditional chemotherapy superior to new alternative for oropharyngeal cancers | News Center
November 16, 2018 - What This Pond Protist Does With Its Genome Will Astound You
November 15, 2018 - Researchers develop tool that speeds up analysis and publication of biomedical data
November 15, 2018 - Scientists identify mechanism used by lung cancer cells to obtain glucose
November 15, 2018 - Abnormalities in development of the brain could be involved in onset of autism, finds new study
November 15, 2018 - Soy protein equally effective as animal protein in building muscle strength
November 15, 2018 - American Academy of Pediatrics, Nov. 2-6
November 15, 2018 - Dopamine drives early addiction to heroin
November 15, 2018 - Variance in gut microbiome in Himalayan populations linked to dietary lifestyle | News Center
November 15, 2018 - Reducing Cardiovascular Disease: The Amish Way
November 15, 2018 - King’s researchers launch charter to guide organizations to engage abuse survivors in research
November 15, 2018 - Enable Injections enters into development agreements with UCB and Apellis Pharmaceuticals
November 15, 2018 - TGen North collaborates with NARBHA Institute to advance human health
November 15, 2018 - Researchers discover molecular basis for therapeutic actions of an African folk medicine
November 15, 2018 - Human Cell Atlas study of early pregnancy shows how mother’s immune system is modified
November 15, 2018 - New guidelines for detecting and managing sarcopenia to be launched in the UK
November 15, 2018 - Researchers explore role of dietary composition on energy expenditure
November 15, 2018 - Elsevier launches Entellect™ Platform, unlocking value by creating AI-ready life sciences data
November 15, 2018 - Now that cannabis is legal in Canada, let’s use it to tackle the opioid crisis
November 15, 2018 - In the Spotlight: At the intersection of tech, health, and ethics
November 15, 2018 - Traditional Glaucoma Test Can Miss Severity of the Disease
November 15, 2018 - Researchers directly connect activities of genes with instinctive behavior in male cichlids
November 15, 2018 - Salk researchers report new methods to identify AD drug candidates with anti-aging properties
November 15, 2018 - St. Jude Hospital announces availability of largest collections of leukemia samples
November 15, 2018 - Attenua Announces First Patient Treated in Phase 2 Clinical Trial in Chronic Cough with Bradanicline
November 15, 2018 - Designing a novel cell-permeable peptide chimera to promote wound healing
November 15, 2018 - NEI investigators combine two imaging modalities to view the retina in unprecedented detail
November 15, 2018 - Determining how hearts develop to better understand congenital heart defects
November 15, 2018 - Maverick immune cells can act independently to identify and kill cancer cells, finds research
November 15, 2018 - Advanced AI and big data methods to tackle dementia
November 15, 2018 - Report reveals increase in pancreatic cancer death rates across Europe
November 15, 2018 - Luxia Scientific announces availability of its gut microbiome test in Luxembourg
November 15, 2018 - New diabetes drugs linked to increased risk of lower-limb amputation and ketoacidosis
November 15, 2018 - New approach targets matrix surrounding neurons to protect neurons after stroke
November 15, 2018 - Lilly Submits New Drug Application to the FDA for Lasmiditan for Acute Treatment of Migraine
November 15, 2018 - Heart failure patients shouldn’t stop meds even if condition improves: study
November 15, 2018 - Parents and carers of people with diabetes experience emotional or mental health problems
November 15, 2018 - RetiPharma secures funding to develop new peptide drug for treating degenerative eye disorders
November 15, 2018 - Breakthrough research could lead to a new wave of cancer-fighting antibodies
November 15, 2018 - Mylan and Biocon launch new insulin glargine biosimilar in the UK
November 15, 2018 - For wildfire safety, only particular masks guard against toxic particulate matter
November 15, 2018 - New study of tribe shows influence of Western diet and lifestyle on blood pressure
November 15, 2018 - Scientists harness power of natural killer cells to treat children with neuroblastoma
November 15, 2018 - Investigating foodborne disease outbreak in Bosnia and Herzegovina based on simulation game
November 15, 2018 - Recommendations Issued for Management of Bradycardia
November 15, 2018 - Benefit unclear due to a lack of suitable studies
November 15, 2018 - TAMEST recognizes UT Southwestern’s Ralph DeBerardinis for changing our understanding of cancer
November 15, 2018 - Researchers discover key factors behind intestinal inflammation in CVID patients
November 15, 2018 - CityU develops first microarrayed 3D neuronal culture platform
November 15, 2018 - Expert suggests ways to control uncomfortable vaginal symptoms in diabetic women
November 15, 2018 - New edition of Red Journal focuses on roles of imaging in radiation oncology
November 15, 2018 - Doctors Aren’t Promoting Breastfeeding’s Cancer-Protection Benefit
November 15, 2018 - Collection of demonstration projects highlights value of patient engagement in research
November 15, 2018 - Technique to ‘listen’ to a patient’s brain during tumour surgery
November 15, 2018 - Seven-year-old returns to life as a “normal, healthy child” following bone marrow transplant
November 15, 2018 - AMSBIO expands range of high quality FFPE cancer cell line controls
November 15, 2018 - Marijuana use by kidney donors has no effect on transplant outcomes
November 15, 2018 - Exploring NMR Spectroscopy Applications through Interesting Infographics
November 15, 2018 - Chapman University wins additional $2.9 million NIH grant to study Alzheimer’s disease
November 15, 2018 - Microgel powder reduces infection and promotes healing
Tiny ‘brains on chips’ reveal mechanisms underlying brain’s wrinkling process

Tiny ‘brains on chips’ reveal mechanisms underlying brain’s wrinkling process

image_pdfDownload PDFimage_print

Being born with a “tabula rasa” – a clean slate – in the case of the brain is something of a curse. Our brains are already wrinkled like walnuts by the time we are born. Babies born without these wrinkles – smooth brain syndrome – suffer from severe developmental deficiencies and their life expectancy is markedly reduced. The gene that causes this syndrome recently helped Weizmann Institute of Science researchers to probe the physical forces that cause the brain’s wrinkles to form. In their findings, reported today in Nature Physics, the researchers describe a method they developed for growing tiny “brains on chips” from human cells that enabled them to track the physical and biological mechanisms underlying the wrinkling process.

Tiny brains grown in the lab from embryonic stem cells – so-called organoids – were pioneered in the last decade by Profs. Yoshiki Sasai in Japan and Juergen Knoblich in Austria. Prof. Orly Reiner of the Institute’s Molecular Genetics Department says that her lab, along with many others, embraced the idea of growing organoids. But Dr. Eyal Karzbrun, in her lab, had to put a bit of a damper on their enthusiasm: The sizes of the organoids they obtained were far from uniform; with no blood vessels, the insides did not have a steady supply of nutrients and started to die; and the thickness of the tissue got in the way of the optical imaging and microscope tracking.

So Karzbrun developed a new approach to growing organoids – one that would enable the group to follow their growth processes in real time: He limited their growth in the vertical axis. This gave him a “pita”-shaped organoid – round and flat with a thin space in the middle. This shape enabled the group to image the thin tissue as it developed and to supply nutrients to all the cells. And by the second week of the tiny “brain’s” growth and development, wrinkles began to appear and then to deepen. Karzbrun: “This is the first time that folding has been observed in organoids, apparently due to the architecture of our system.”

Karzbrun is a physicist by training, and he naturally turned to physical models for the behavior of elastic materials to understand the formation of the wrinkles. Folds or wrinkles in a surface are the result of mechanical instability – compression forces applied to some part of the material. So for example, if there is uneven expansion in one part of the material, another part might be forced to fold in order to accommodate the pressure. In the organoids, the scientists found such mechanical instability in two places: The cytoskeleton – the internal skeleton – of the cells in the center of the organoid contracted; and the nuclei of the cells near the surface expanded. Or, to think of it another way, the outside of the “pita” grew faster than its inside.

While this achievement was impressive, Reiner was not convinced that the wrinkles in the organoids were really modeling the folds in a developing brain. So the group grew new organoids, this time bearing the same mutations carried by babies with smooth brain syndrome. Reiner had identified this gene – LIS1 – back in 1993, and has investigated its role in the developing brain and in the disease, which affects one in 30,000 births. Among other things, the gene is involved in the migration of nerve cells to the brain during embryonic development, and it also regulates the cytoskeleton and molecular motors in the cell.

The organoids with the mutated gene grew to the same proportions as the others, but they developed few folds and the ones they did develop were very different in shape from the normal wrinkles. Working on the assumption that differences in the physical properties of the cell were responsible for these variations, the group investigated the organoid’s cells with atomic force microscopy, with the help of Dr. Sidney Cohen of the Chemical Research Support Department. By measures of elasticity, the normal cells were about twice as stiff as the mutated ones, which were basically soft. Reiner: “We discovered a significant difference in the physical properties of cells in the two organoids, but we observed difference in their biological properties as well. For example, the nuclei in the centers of the mutant organoids moved more slowly, and we saw significant differences in gene expression.”

Even before the paper’s publishing date, the scientific community has been showing great interest in this new approach to growing organoids. “It is not exactly a brain, but it is quite a good model for brain development,” says Reiner. “We now have a much better understanding of what makes a brain wrinkled or, in cases of those with one mutated gene, smooth.” The researchers plan to continue developing their approach, which they believe could lead to new insights into other disorders that are tied to brain development, including microcephaly, epilepsy and schizophrenia.

Also participating in this research were Prof. Yaqub Hanna, who assisted with growing the embryonic stem cells, and research student Aditya Kshirsagar in Reiner’s group.

Source:

https://wis-wander.weizmann.ac.il/life-sciences/%E2%80%9Cbrain-chip%E2%80%9D-reveals-how-brain-folds

Tagged with:

About author

Related Articles