Transit-amplifying neuroblast lineages in the larval brain
Throughout embryonic and larval development, neural precursor cells called neuroblasts divide in a self-renewing manner and produce large numbers of small, differentiating daughter cells. These daughter cells eventually give rise to the neurons and glia of the central nervous system. It was previously thought that all neuroblast daughters are ganglion mother cells (GMCs) — cells that divide terminally to produce differentiated neurons or glia. We found that a distinct subpopulation of larval neuroblasts do not produce ganglion mother cells, but instead generate small, secondary neuroblasts. The secondary neuroblast acts as an intermediate precursor, dividing several times to give rise to multiple GMCs. Adding this transit-amplification step to the neuroblast lineage allows production of GMCs and neurons at a faster rate.
In these complementary images of a single larval brain lobe, primary neuroblasts appear as large circles outlined by phalloidin staining (left, green; right, blue). Primary neuroblasts of the classical lineages express the neural precursor marker Asense (red). An asensereporter (green, right, asense-Gal4 » CD8-GFP) is also expressed in the classical neuroblast and many of its progeny. By contrast, primary neuroblasts of the transit-amplifying lineages do not express Asense or the asense reporter. The asense reporter is not detectable in small secondary neuroblasts (right), even though they express Asense protein.
Xenopus laevis oocytes | wellcome images
Stage V-VI Xenopus laevis oocytes surrounded by thousands of follicle cells, as visualized by Hoechst staining.
Edit: red eyed tree frog embryos
Thanks to the eagle eyes of yaminatori
The first images have been captured of the fetal brain at different stages of its development. The work gives a glimpse of how the brain’s neural connections form in the womb, and could one day lead to prenatal diagnosis and treatment of conditions such as autism and schizophrenia.
We know little about how the fetal brain grows and functions – not only because it is so small, says Moriah Thomason of Wayne State University in Detroit, but also because “a fetus is doing backflips as we scan it”, making it tricky to get a usable result.
Undeterred, Thomason’s team made a series of functional magnetic resonance imaging (fMRI) scans of the brains of 25 fetuses between 24 and 38 weeks old. Each scan lasted just over 10 minutes, and the team kept only the images taken when the fetus was relatively still.
The researchers used the scans to look at two well-understood features of the developing brain: the spacing of neural connections and the time at which they developed. As expected, the two halves of the fetal brain formed denser and more numerous connections between themselves from one week to the next. The connections tended to begin in the middle of the brain and spread outward as the brain continued to develop.
Thomason says that the team is now scanning up to 100 fetuses at different stages of development. These scans might allow them to start to see variation between individuals. They are also applying algorithms to the scanning program that will help correct for the fetus’s movements, so fewer scans will be needed in future.
Once they understand what a normal fetal brain looks like, the researchers hope to study brains that are forming abnormal connections. Disorders such as schizophrenia or autism, for instance, are believed to start during development and might be due to faulty brain connections. Understanding the patterns that characterise these diseases might one day allow physicians to spot early warning signs and intervene sooner. Just as importantly, such images might improve our understanding of how these conditions develop in the first place, Thomason says.
Emi Takahashi of Boston Children’s Hospital says that one way to do this would be to follow a large group of children after they are born, and look back at the prenatal scans of those who later develop a brain disorder. Although she says the study is a very good first step, understanding the miswiring of the brain is so difficult that it may be some time before the results of such work become useful in clinical settings.
(Images: Leicester University/Rex Features)
Doubts remain that the Leicester body is Richard III
Hacked, sliced, stripped, slung over a horse and stabbed in the bottom. Tradition tells us that Richard III - the last Plantagenet king of England - met an especially bloody end in the battle of Bosworth Field on 22 August 1485. Now we may have a body to go with the legend.
Anticipation started building last year when an interesting skeleton was unearthed from beneath a car park in Leicester, UK. Today a team of researchers from the University of Leicester announced that, “beyond reasonable doubt”, the body is that of Richard III. They draw on multiple strands of evidence to back their claim: as well as the expected wounds, the skeleton shows signs of scoliosis, a disease that curves the spine, which fits with accounts of the king being “hunchbacked”.
But the clincher - for the researchers, at least - is newly revealed DNA evidence from two of Richard’s living maternal descendants.
Michael Ibsen, a furniture-maker originally from London, and his distant cousin, who wishes to remain anonymous, were tracked down using genealogical records. Geneticist Turi King of the University of Leicester then matched traces of mitochondrial DNA extracted from the skeleton with samples taken from the purported relatives. Since Ibsen and his cousin are both the last of their lines, this could have been the last chance for such evidence to be obtained.
Mitochondrial DNA is passed down the maternal line and has 16,000 base pairs in total. Typically, you might expect to get 50 to 150 fragments from a 500-year-old skeleton, says Ian Barnes at Royal Holloway, University of London, who was not involved in the research. “You’d want to get sequences from lots of those fragments,” he says. “There’s a possibility of mitochondrial mutations arising in the line from Richard III.”
“It’s intriguing to be sure,” says Mark Thomas at University College London. It is right that they used mitochondrial DNA based on the maternal line, he says, since genealogical evidence for the paternal lineage cannot be trusted.
But mitochondrial DNA is not especially good for pinpointing identity. “I could have the same mitochondrial DNA as Richard III and not be related to him,” says Thomas.
The researchers used the two living descendents to “triangulate” the DNA results. The evidence will rest on whether Ibsen and his cousin have sufficiently rare mtDNA to make it unlikely that they both match the dead king by chance.
They must also not be too closely related. If Richard III’s living descendants shared a common female ancestor even 150 years ago, their DNA could still be too close for the pair to count as distinct samples, says Thomas.
We’ll have to wait for the results to be published to know for sure, says Barnes.
The study, carried out in mice, found that in the early stages of infection, M. leprae were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells.
Like typical stem cells, these cells were pluripotent, meaning they could then become other cell types, for instance muscle cells. This enabled M. leprae to spread to tissues in the body.
The study, published in the journal Cell, also shows that the bacteria-generated stem cells have unexpected characteristic. They can secrete specialized proteins – called chemokines – that attract immune cells, which in turn pick up the bacteria and spread the infection.
“We have found a new weapon in a bacteria’s armory that enables them to spread effectively in the body by converting infected cells to stem cells. Greater understanding of how this occurs could help research to diagnose bacterial infectious diseases, such as leprosy, much earlier,” said study lead author Prof Anura Rambukkana, Medical Research Council Center for Regenerative Medicine at the University of Edinburgh.
“This is very intriguing as it is the first time that we have seen that functional adult tissue cells can be reprogrammed into stem cells by natural bacterial infection, which also does not carry the risk of creating tumorous cells. Potentially you could use the bacteria to change the flexibility of cells, turning them into stem cells and then use the standard antibiotics to kill the bacteria completely so that the cells could then be transplanted safely to tissue that has been damaged by degenerative disease.”
Dr Rob Buckle, Head of Regenerative Medicine at the Medical Research Council Center for Regenerative Medicine at the University of Edinburgh, said: “this ground-breaking new research shows that bacteria are able to sneak under the radar of the immune system by hijacking a naturally occurring mechanism to ‘reprogramme’ cells to make them look and behave like stem cells. This discovery is important not just for our understanding and treatment of bacterial disease, but for the rapidly progressing field of regenerative medicine. In future, this knowledge may help scientists to improve the safety and utility of lab-produced pluripotent stem cells and help drive the development of new regenerative therapies for a range of human diseases, which are currently impossible to treat.”
The scientists believe mechanisms used by leprosy bacteria could exist in other infectious diseases. Knowledge of this newly discovered tactic used by bacteria to spread infection could help research to improve treatments and earlier diagnosis of infectious diseases.
A nice video showing the transcription of DNA to mRNA by RNA-polymerase. A messenger RNA transcript then exists the nucleus to find a ribosome. Their is it translated into a primary structure polynucleotide. Chaperonin fold proteins with the use of ATP into secondary and tertiary structures. Once realised from the chaperonin the protein may be complete or join part of a quaternary structure.