Breaking News
June 19, 2018 - Study combines gene editing and stem cell technologies to predict person’s risk for heart disease
June 19, 2018 - Weight loss of 20% or greater results in better outcomes for overweight, obese adults with knee osteoarthritis
June 19, 2018 - Alnylam Reports Updated Positive Results from Phase 1/2 Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1 (PH1)
June 19, 2018 - Study predicts most people with earliest Alzheimer’s signs won’t develop dementia associated with the disease
June 19, 2018 - Abnormal sleep duration linked to metabolic syndrome in new study
June 19, 2018 - Researchers develop new method to preserve fertility in boys with prepubertal cancer
June 19, 2018 - Late onset of diabetes could be indicative of pancreatic cancer
June 19, 2018 - Skin tone makes big difference in diagnosis and treatment of dermatologic conditions
June 19, 2018 - After addiction, the long road back to good health
June 19, 2018 - High blood pressure could be an early sign of dementia
June 19, 2018 - Innovative drugs and new European treatment guidelines refine, improve MS therapy
June 19, 2018 - BIDMC scientists develop new tool to benefit patients with HCV-associated liver failure
June 19, 2018 - Diabetes diagnosis may come with increased risk of pancreatic cancer for African-Americans, Latinos
June 19, 2018 - Personalized Goals, Cash Motivate Heart Patients to Exercise
June 19, 2018 - Nipah Virus (NiV) | CDC
June 19, 2018 - Genomics offers new treatment options for infants with range of soft tissue tumors
June 18, 2018 - Study shows how moderate consumption of alcohol can protect the heart
June 18, 2018 - Gene editing technology predicts heart disease risk
June 18, 2018 - Who Will and Who Won’t Get the Flu?
June 18, 2018 - Research shows effective responses to online feedback
June 18, 2018 - Scientists to focus on big data and genetics to identify risk factors for dementia
June 18, 2018 - Ultrasound-based technology for assessing overweight adolescents with liver disease
June 18, 2018 - Osteochondral knee defect treated using cell technology
June 18, 2018 - New clinical trial finds no evidence to support use of tamsulosin for kidney stones
June 18, 2018 - Study demonstrates increased levels of gum disease in people at risk of rheumatoid arthritis
June 18, 2018 - Ebola & Marburg | NIH: National Institute of Allergy and Infectious Diseases
June 18, 2018 - Brains, eyes, testes: off-limits for transplants?
June 18, 2018 - Drug used to treat myelofibrosis can awaken ‘dormant’ lymphomas in the bone marrow
June 18, 2018 - New study focuses on best, cost effective practices to bridge treatment gap for brain disorders
June 18, 2018 - New study highlights predictors that prevent from achieving remission in early RA
June 18, 2018 - Neuroscientists map feeling of cool touch to the brain’s insula in mouse model
June 18, 2018 - Study highlights potential use of blood biomarkers as diagnostic tool for sleep apnea
June 18, 2018 - Eating plant-based diet can reduce risk for heart problems in people with type 2 diabetes
June 18, 2018 - Lenabasum has acceptable safety and tolerability in diffuse cutaneous systemic sclerosis
June 18, 2018 - Study shows link between risky opioid prescriptions and increased odds of death
June 18, 2018 - Bone density scans could help determine likelihood of cardiovascular disease
June 18, 2018 - Mechanical thrombectomy appears to be important therapy for acute stroke in very old patients
June 18, 2018 - Novel compound as effective as FDA-approved antibiotics for treating deadly infections
June 18, 2018 - Ironwood Pharmaceuticals Announces FDA Orphan Drug Designation for Olinciguat for the Treatment of Sickle Cell Disease
June 18, 2018 - Surgical outcomes equivalent whether physician anesthesiologist assisted by nurse anesthetist or AA
June 18, 2018 - Studies provide insight into molecular changes prior to onset of arthritis
June 18, 2018 - Dyaco unveils specialist medical and rehabilitation equipment range in the UK
June 18, 2018 - Engineers develop algorithm to monitor joints of patients with arthritis
June 18, 2018 - Women with higher vitamin D blood levels have lower risk for breast cancer
June 18, 2018 - New studies help elucidate role of sleep in chronic pain
June 18, 2018 - Researchers link red meat sensitivity spread by ticks with heart disease
June 18, 2018 - Research explores role of autopsy in cardiovascular medicine
June 18, 2018 - Motif Bio Submits NDA for Iclaprim
June 18, 2018 - NIH-funded researchers identify target for chikungunya treatment
June 18, 2018 - Negative emotions are murkier, less distinct in adolescence
June 18, 2018 - Gut microbiome may be potential contributor to depression, anxiety in people with obesity
June 18, 2018 - Canakinumab reduces gout rate by more than half in atherosclerosis patients, study shows
June 18, 2018 - What Does the Future Hold?
June 18, 2018 - FDA Approves Keytruda (pembrolizumab) for Treatment of Refractory or Relapsed Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
June 18, 2018 - School cliques don’t always click
June 18, 2018 - Three experts from The Tinnitus Clinic contribute to major review on pulsatile tinnitus
June 18, 2018 - Unwieldy health costs often stand between teachers and fatter paychecks
June 18, 2018 - Link between frailty and mortality remains unchanged despite lower death rates, study finds
June 18, 2018 - Sleep disorders appear to be first sign of serious neurological diseases
June 18, 2018 - Childhood, adult obesity raise risk of developing hip and knee osteoarthritis
June 18, 2018 - Study unravels ‘blood stem cell niche’ puzzle
June 18, 2018 - People with heart problems do not take enough exercise, shows study
June 18, 2018 - Strong Link Identified Between T2DM and Parkinson’s Disease
June 18, 2018 - Early childhood interventions show mixed results on child development
June 18, 2018 - Chronic use of opioids related to increased risk of fracture nonunion
June 18, 2018 - AHA: Family Perseveres After Losing Father to Heart Attack
June 18, 2018 - Oral propranolol seems safe for infantile hemangioma
June 18, 2018 - New study gives explanation for food’s prominence in memory
June 18, 2018 - First photoactive drug to fight Parkinson’s disease
June 18, 2018 - Patient’s self-evaluation of personality disorders not as far off as previously perceived
June 18, 2018 - Upadacitinib Monotherapy Meets All Primary and Ranked Secondary Endpoints Versus Methotrexate in a Phase 3 Study in Rheumatoid Arthritis
June 18, 2018 - Vitamin B3 has a positive effect on damaged nerve cells in Parkinson’s patients
June 17, 2018 - Sunovion Announces FDA Acceptance of New Drug Application for Apomorphine Sublingual Film (APL-130277)
June 17, 2018 - Bid to beat obesity focuses on fat that keeps us warm
June 17, 2018 - Work Stress May Increase Risk of Developing Atrial Fibrillation
June 17, 2018 - New Zealand’s secret recipe for active school travel: The neighborhood built environment
June 17, 2018 - New Medscape report reveals sexual harassment rate of physicians
June 17, 2018 - Surgical Blood Transfusions Tied to Clot Risk
June 17, 2018 - CDC chief makes $375K, far exceeding his predecessors’ pay
June 17, 2018 - Education linked to higher risk of short-sightedness
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