Dubbed as “rosehip neuron“, a new brain neuron recently discovered is unique based on its morphology and the set of genes it activates. Neuroscientists recently uncovered this new type of neuron from postmortem human brain samples. They presumed that this rosehip neuron occurs in the brain of humans but not in rodents.
Rosehip neurons found in human brains
What makes human brain special? What sets it apart from other animal brains? Humans have this sort of consciousness and intelligence that make them different from other species. Apart from the complexity and the size of the human brain, its cellular components seem to be different from that of the other animals. Neuroscientists found rosehip neurons in human brain. These cells have not yet been observed in the brains of mice and other well-studied laboratory animals. Researchers reported this recent discovery in Nature Neuroscience.1 Nevertheless, they were fast to warn not to make haste assumptions. The rosehip neurons may not be unique to humans. More studies are on the way to confirm it.
What their findings implicate is the suitability of rodent brains as experimental models. Rodent brains lack such neurons. Thus, they may not be fit as laboratory models, especially when one tries to understand human neurologic diseases and how the brain works.
Current info on human rosehip neurons
Since rosehip neurons are a recent discovery, there is currently little information about them. What the neuroscientists know is they appear bushy. In fact, their bushy appearance accounts for their name “rosehip“. Rosehip originally refers to the accessory fruit of the rose plant. The rosehip neuron looks like the accessory fruit of the rose after petals are shed.
Researchers discovered the rosehip neurons from the top layer of the cortex of the brain from the postmortem brains of two men in their 50s. The rosehip neuron belongs to a group of inhibitory neurons. This means that it works by inhibiting other neuronal activity in the brain.
Researchers from the Allen Institute collaborated with the J. Craig Venter Institute. They found that the rosehip neurons seemed to have a different genetic signature. The rosehip neurons turned on a unique set of genes. They also formed synapses with pyramidal neurons. Pyramidal neurons are a different type of brain cells named after their shape.
Future research on rosehip neurons
Researchers have yet to fully recognize the purpose and importance of rosehip neurons in the human brain. In doing so, they may gain a significant insight regarding their role in neurologic function and diseases. They also aim to check the presence of rosehip neurons in other human brain parts as well as in the brains of other animals. Details on their recent work on rosehip neurons is published in Nature Neuroscience.2
— written by Maria Victoria Gonzaga based on the news release and materials from the Allen Institute website
1 Allen Institute. (27 Aug. 2018). Scientists identify a new kind of human brain cell. Retrieved from http://www.alleninstitute.org/what-we-do/brain-science/news-press/articles/scientists-identify-new-kind-human-brain-cell
2 Boldog, E. et al. (2018). Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type. Nature Neuroscience. DOI: 10.1038/s41593-018-0205-2
Scientists are excited over a gene-silencing drug that recently won an approval from the US Food and Drug Administration (FDA). This approval is historic because it is the first of its kind. The drug works by silencing genes that otherwise lead to the production of damaged proteins associated with certain diseases. The drug is called patisiran and it recently got its approval for use to treat the hereditary transthyretin amyloidosis, a fatal rare hereditary condition associated with damaged nerves.
Gene basis of hereditary transthyretin amyloidosis
The hereditary transthyretin amyloidosis is a rare and fatal hereditary condition that manifests as an autosomal dominant neurodegenerative disease. Because it is dominant, this means that the offspring inheriting the defective autosomal gene will acquire the condition. A defective transthyretin (TTR) gene located on human chromosome 18q12.11 is the genetic cause. The most common type of mutation is the replacement of valine by methionine at position 30.
A normal, functional TTR gene codes for transthyretin (TTR) protein that is involved in the transportation of thyroxine (thyroid hormone) and retinol (vitamin A). TTR protein is produced mainly in the liver, and is then secreted into the bloodstream. TTR proteins from a defective TTR gene tend to misfold and stick together, forming amyloids. This building-up of amyloids in tissues is called amyloidosis. In hereditary transthyretin amyloidosis, pathogenic amyloids form especially in the peripheral nervous system, which may eventually lead to a progressive sensory and motor polyneuropathy.
Gene silencing by RNA interference
Normally, the cell performs what is now known as RNA interference (RNAi). It is also known as quelling, co-suppression, and post-transcriptional gene silencing. In this process, the RNA molecules inhibit the translation of a gene. They do so when they neutralize targeted mRNA molecules. RNAi is different from CRISPR, which is a gene-editing tool that makes use of a guide RNA. CRISPR is used to switch off a gene and has a potential therapeutic use to treat cancers. It also had FDA approval in 2016 for use in a clinical trial study. However, recent studies on CRISPR raised issues about its safety since it was found to cause unexpected mutations that involve large deletions and complex genomic rearrangement at target sites.2 To learn more about CRISPR, read: CRISPR caused gene damage? … Unlike CRISPR, the RNAi is presumed not to bring permanent changes to DNA.3
Patisiran as gene-silencing drug
Patisiran is RNA-based drug that recently received the first FDA approval for use as a gene-silencing tool. People with hereditary transthyretin-mediated amyloidosis can now be treated with it. The drug interferes with the production of transthyretin. It doses so by preventing the mRNA involved in the translation of the gene that codes for the problematic protein. This is good news to people with such fatal rare condition. FDA has now approved a drug that can be administered to them. The downside, though, is the chillingly high cost. The cost of the therapy is estimated to be about $450,000 in a year.4
New therapeutic technologies that delve into the molecular and gene mechanisms hold so much promise especially in conditions that until now lack an efficacious treatment. RNAi is a precise gene-silencing tool and scientists are excited in its historic FDA approval. This means that it is a glorious start for contemporary therapies involving targeted gene silencing and alterations. The cost of the therapy may be encumbering but it is still a step forward, certainly a scientific feat to reckon.
— written by Maria Victoria Gonzaga
1 TRANSTHYRETIN; TTR. (n.d.). OMIM.org. Retrieved from https://omim.org/entry/176300
2 Gonzaga, M. V. (17 July 2018). CRISPR caused gene damage? Rise and pitfall of the gene-editor. Biology-Online.org. Retrieved from https://www.biology-online.org/crispr-caused-gene-damage-rise-pitfall-gene-editor/
3 Nield, D. (14 Aug. 2018). A First of Its Kind Gene-Silencing Drug Just Got Historic Approval From The FDA. ScienceAlert. Retrieved from https://www.sciencealert.com/first-drug-silencing-genes-approved-by-fda-for-disease-treatment
4 Lipschultz, B. & Cortez, M. (10 Aug. 2018). Rare-Disease Treatment From Alnylam to Cost $450,000 a Year. Bloomberg. Retrieved from https://www.bloomberg.com/news/articles/2018-08-10/alnylam-wins-first-u-s-drug-approval-in-rare-genetic-disease
Scientists from Cardiff University’s School of Biosciences reported that a father’s gene may have an impact on the quality of care that is furnished by the mother to her newborn offspring. One of the most crucial roles of a mother is being able to provide and attend to the needs of her offspring, especially during the time of conception up to the time of nursing the offspring. Good quality maternal care is essential to ensure a healthy development of the newborn and the recent study on mice suggests that a father’s gene may have an effect on the mother’s nurturing behavior towards her offspring before and after they are born.
Imprinting of genes
In humans, the zygote is a diploid cell that results from the union of two haploid sex cells. This means that the zygote will possess two copies of the genome, i.e. one coming from the mother and the other one from the father. The autosomal genes of the zygote would therefore occur in pairs or as two copies. Their expressions occur simultaneously except for a few genes whose expressions will depend on the parent-of-origin. Depending on the parent source, one of the gene copies will be imprinted, which means it will be ”silent”. For example, a father’s gene that is imprinted will be “silent” and will not be expressed but the other copy of the gene (from the mother) will be expressed, or “vice versa“. This phenomenon is called genomic imprinting. An imprinted gene is one in which the DNA is methylated. A methylated gene means that its expression is suppressed.1
Phlda2 gene – overview
Pleckstrin homology-like domain family A member 2 (Phlda2) gene is an example of a gene whose expression accords to the phenomenon of genomic imprinting. The gene is located in the cluster of imprinted genes on chromosome 11p15.5.2 It encodes for the Phlda2 protein. It was also found that only one copy of the Phlda2 gene is “switched on” and that the other copy of the gene that is “silent” comes from the father.3 In rodents, one of its physiological roles is identified to be associated with the regulation of the activity of the placental cells called spongiotrophoblasts, which are cells responsible for the production of placental hormones. It was reported that the Phlda2 gene controls their size, and therefore their hormone production activity. 3
Phlda2 gene – impact on mother’s behavior
Scientists from Cardiff University’s School of Biosciences found that female mice carrying pup embryos with two active Phlda2 genes, and thus with relatively higher Phlda2 levels and probably reduced placental hormone activity, exhibited decreased nursing and grooming of pups but with an increased focus in nest building. On the contrary, mothers carrying pup embryos with lower Phlda2 levels were more focused at nurturing their pups than on nest building. They also identified corresponding changes in the brain regions essential for maternal care behavior (particularly, hippocampus and hypothalamus) of the mothers during pregnancy. Their findings implicate that the Phlda2 gene activity may have an effect on the maternal care behavior of mice.3
Based on the recent findings, scientists speculate that Phlda2 gene activity may also have an impact in human pregnancies. Many regard motherhood as an epitome of a woman’s existence. Apparently, there are instances when the quality of maternal care provided to the child is inadequate due to various factors. If these findings are relevant to humans, then, this is a potential aspect to probe in order to understand the biology of maternal care behavior – one that involves Phlda2 gene.
— written by Maria Victoria Gonzaga
1 Genomic imprinting. (n.d.). Biology-Online Dictionary. Retrieved from https://www.biology-online.org/dictionary/Genomic_imprinting
2 PHLDA2 pleckstrin homology like domain family A member 2 [Homo sapiens (human)]. (8 July 2018). National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved from https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7262
3 Creeth, H.D.J., McNamara, G.I., Tunster, S.J., Boque-Sastre, R., Allen, B., Sumption, L., et al. (2018). Maternal care boosted by paternal imprinting in mammals. PLoS Biol, DOI: 10.1371/journal.pbio.2006599
CRISPR as a gene editing tool made a prodigious leap forward in science. In 2015, it was heralded as Science’s 2015 Breakthrough of the Year.1 It stymied other impressive contenders like Ebola vaccine. It supersedes other gene-editing predecessors, such as TALENs (transcription activator-like effector nucleases) and ZFNs (zinc finger nucleases). Unlike these two, CRISPR does not need a custom protein for every targeted DNA sequence. It does, however, require a guide RNA (gRNA). Even so, the process of designing a gRNA is easier and less time-consuming than creating a custom protein. For that, it is favoured over other gene-editing tools.
The rise of a revolutionary gene-editing tool — CRISPR
The discovery of CRISPR was indeed phenomenal. Short for clustered regularly interspaced short palindromic repeats, CRISPR swiftly opened avenues for biological and medical innovations. Initially identified as a family of viral DNA snippets, it was discovered to inherently protect bacteria against re-invading bacteriophages akin to our immune system’s adaptive immunity. This natural gene-editing system in bacteria has two key players: gRNA and Cas9 (CRISPR-associated enzyme). The gRNA finds and binds to specific DNA target. The Cas9 goes where the gRNA is, and then cuts the DNA target, disabling the latter. Now, scientists exploit it as a way to splice specific DNA targets and then replace them with a DNA that would yield the desired outcome. For instance, CRISPR can be used to correct physiological anomalies caused by gene mutations or defective genes.
CRISPR – a versatile gene-editing tool
CRISPR has been shown to have the potential to slow down the progression of cancers. It can switch off a gene in immune cells. The altered immune cells can be designed to fight cancer. In 2016, US FDA approved the clinical trial study where CRISPR technology would be used to cure patients with cancers. 2 Not only in biology and medicine, the use of CRISPR has also extended to agriculture and animal husbandry. Through it, the genes of crops and livestock can be improved. They can be made more resistant to certain diseases.
CRISPR causing gene damage?
One of the issues raised against CRISPR is ethical concerns. Similar to what was ethically raised against other gene-editing technologies, the concern is chiefly about the notion of bias and “playing God”. What are the standards that will define and permit judgment over a gene to be construed as either “good” or “bad”? But taking aside this issue, there is another issue being hurled against CRISPR. Marked of recent as “breaking news”, a study published in Nature warned about the possible pathogenic consequences of CRISPR when the researchers identified on-target mutagenesis in the form of large deletions and complex genomic rearrangements at target sites in mitotically active cells of mice and humans.3 This is not the first time that a study questioned the safety of CRISPR technology. In 2017, researchers from Columbia University reported that it led to hundreds of unexpected mutations. Nevertheless, this claim was retracted when they failed to replicate their results.4
CRISPR as a gene-editing tool wields so much potential beyond one can imagine. It is easy to use, feasible, and far-reaching. One can expect that issues would come along the way, and thus slow down its fast-paced utilization in different fields. It is a no-nonsense stumbling block for we belong in a community that moves forward through social discourse fueled by scientific nosiness and reasoning. Probing the dangers of CRISPR should be as extensive as exploring its benefits. We must be not too quick to adulate without first bringing out in the open its risks — especially ones that are as crucial as mutations and gene damage.
— written by Maria Victoria Gonzaga
1 Science News Staff. (2015). And Science’s 2015 Breakthrough of the Year is…
ScienceMag.org. Retrieved from http://www.sciencemag.org/news/2015/12/and-science-s-2015-breakthrough-year
2 Reardon, S. (2016). First CRISPR clinical trial gets green light from US panel. Retrieved from
3 Kosicki, M., Tomberg, K. & Bradley, A. (2018 July 16). Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nature Biotechnology. https://doi.org/10.1038/nbt.4192
4 Dockrill, P. (2018 July 16). BREAKING: CRISPR Could Be Causing Extensive Mutations And Genetic Damage After All. ScienceAlert.com. Retrieved from https://www.sciencealert.com/crispr-editing-causes-frequent-extensive-mutations-genetic-damage-target-deletion-site
Jumping genes, also known as transposons, are gaining momentum. They are considered either as slacking junks or maleficent parasites in our genome. As such, they are largely taken for granted. However, it seems the tables have turned. There seem to be certain jumping genes that without them we would not move past our embryonic state. Researchers from the University of California – San Francisco presented proof that certain jumping genes do perform a crucial role during the development of an embryo. Without them, the embryo would not progress as it should.1
Jumping genes — junk DNAs
Transposons are small segments of DNA with a special capability. They create copies of the genetic material and then insert at random sites in the genome.2 For that, they are dubbed as “jumping genes” based on the “jumping” activities that they do. Some consider jumping genes as junk DNA because they tend to replicate needlessly multiple copies of DNAs that already exist. Some of these genetic copies could be noncoding (junk) DNAs. Our genome is comprised mostly of junk — about 98-99%! Only 1 or 2 % of it codes for the building blocks of proteins. Scientists presumed that these noncoding regions are unnecessary and therefore viewed as an evolutionary mess in our genome. Apparently, half of our genome is comprised of jumping genes, and the most common is the long interspersed nuclear element-1 (LINE1).1
Jumping genes — parasitic stowaways
While some people view jumping genes as slackers that add up to the pile of junk littering our genome, others see them as parasitic stowaways. Because they can “jump” at seemingly random sites in the genome, they could insert themselves where they might cause gene disruptions, deleterious mutations, and chromosomal rearrangements resulting in diseases, including cancer.3
LINE1 — a paradoxical jumping gene
Researchers from the University of California – San Francisco recently reported that LINE1 (a jumping gene) is crucial during embryonic development. LINE1 accounts for 20% or more of the human genome. It is a retrotransposon, meaning it is amplified by first transcribing a segment of DNA into RNA, and then reverse-transcribed into DNA. The extra DNA copy will then be inserted at a different site in the genome.2 This jumping gene apparently acts as a critical regulator during the early embryonic development. It appears indispensable for an embryo to develop past the two-cell stage.1 This finding seems paradoxical since LINE1 has been implicated in various diseases, particularly cancers.4 Nevertheless, the important role of LINE1 was revealed when it was eliminated from the fertilized eggs, and consequently, they all remained at the two-cell phase. Accordingly, the role of the jumping gene in embryonic development is associated with the LINE1 RNA forming a complex with Nucleolin and Kap1 (gene regulatory proteins). The complex is believed to regulate embryonic development by turning off the dominant genes orchestrating the embryo’s two-cell state as well as by turning on the genes that promote further cell divisions and development.1
Jumping genes are mostly underappreciated largely because they are believed to be contributors to a pile of genetic junk or as parasitic stowaways. Despite being regarded as such, recent findings poised them as crucial genes. While most studies focus on the 1-2% of the genome performing a blatantly important role, i.e. to code for amino acids whereby a protein could be spectacularly built from, the recent study implicates that the jumping genes, too, deserve a spot in the research field.
— written by Maria Victoria Gonzaga
1 University of California – San Francisco. (2018, June 21). Not junk: ‘Jumping gene’ is critical for early embryo: Gene that makes up a fifth of the human genome is not a parasite, but key to the first stages of embryonic development. ScienceDaily. Retrieved from www.sciencedaily.com/releases/2018/06/180621141038.htm
2 Transposon. (n.d.). Biology-Online Dictionary. Retrieved from https://biology-online.org/dictionary/Transposon
3 Chénais, B. (2013). Transposable elements and human cancer: A causal relationship? Biochimica et Biophysica Acta (BBA) – Reviews on Cancer, 1835 (1), 28-35. https://doi.org/10.1016/j.bbcan.2012.09.001
4 Burns, K. H. (2017). Transposable elements in cancer. Nature Reviews Cancer, 17, 415–424. https://www.nature.com/articles/nrc.2017.35