Fruit fly lights up brain wiring

Fruit fly lights up brain wiring
A strain of flies was generated with fluorescent brain cells

(Medical Xpress)—Fluorescent fruit flies have helped University of Queensland researchers take a critical step toward understanding the human brain's neuronal "wiring" and how it can go awry.

Study leader Dr Sean Millard, from UQ's School of Biomedical Sciences, said neurobiologists had been baffled by how a small number of genes controlled billions of specific connections in the brain.

"This is a central question in neurobiology that is critical for understanding how arise," Dr Millard said.

A strain of flies was generated with fluorescent that reported which brain cells expressed two forms of a Down Syndrome protein, Dscam2, that has been implicated in brain disorders.

Dr Millard said disorders, including Down Syndrome and autism, were characterised by miswired neural connections, and the discovery brought researchers closer to understanding how these occurred.

"This study shows that a single gene produces different forms of the same protein in different neurons," he said.

"Neuron-specific expression of different Dscam2 proteins was shown to be necessary for proper neuronal wiring."

Dr Millard said the discovery could be vital in understanding how the brain made so many specific connections using such a small toolkit of genes.

"The study provides the first example of how different types of cells require different versions of the same protein for normal brain wiring," he said.

"This process, called , allows a single gene to generate multiple protein products, called isoforms, with distinct properties.

"As most human genes undergo alternative splicing, it has long been hypothesised that this is one of the key mechanisms for increasing the repertoire of proteins that generate specific connections between brain cells.

"However, direct evidence for cell-specific alternative splicing was lacking until this discovery."

Fluorescent strains of flies were generated that reported which cells expressed the two different forms of the protein.

"This research implicates alternative splicing as a cellular process that may be perturbed in disorders," he said. 

The study appears in the neuroscience publication Neuron.

Explore further

Mechanism explains complex brain wiring

More information: "Cell-Specific Alternative Splicing of Drosophila Dscam2 Is Crucial for Proper Neuronal Wiring." Neuron, Volume 83, Issue 6, p1376–1388, 17 September 2014. DOI:
Journal information: Neuron

Citation: Fruit fly lights up brain wiring (2014, October 30) retrieved 13 October 2019 from
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Oct 30, 2014
Excerpt: "However, direct evidence for cell-specific alternative splicing was lacking until this discovery."

My comment: Cell-type specific alternative splicings of pre-mRNAs link RNA-directed DNA methylation to RNA-mediated events and amino acid substitutions that differentiate all cell types in all individuals of all species. That was the the focus of my 2013 review based on our 1996 review that focussed on sex differences in cell types in a section on molecular epigenetics.

Co-author TB wrote: "Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans..."


See also: Cell-intrinsic requirement of Dscam1 isoform diversity for axon collateral formation http://www.scienc...abstract

Oct 31, 2014
We have:

A single gene, doublesex, controls wing mimicry in butterflies

"Marcus Kronforst, Neubauer Family Assistant Professor of Ecology & Evolution at the University of Chicago and senior author of the study. "But in this case, it's just this one. This single gene that controls sexual differentiation has been co-opted to do a totally new job."

Read more at:

and we have:
Scientists unravel the genetic secrets of nature's master of mimicry

Dr Martijn Timmermans of Imperial College London, who led the study, said: "The wings of the Mocker Swallowtails have bewildered biologists for almost a century. By pinpointing the switch, we have revealed a unique mechanism. It is really exciting to show that all this diversity is determined by variation in just a single gene."

Read more at:


Oct 31, 2014
continued from last link above:

The genetic switch appears to be the gene called 'engrailed', a gene previously shown to be important in patterning the early embryo of fruit flies. The engrailed gene belongs to a family of genes called transcription factors that switch on networks of genes responsible for all aspects of development.

Previously the engrailed gene has been shown to be important in setting up patterning in developing fruit fly embryos, however, nature seems to have redeployed this gene into much later patterning – the patterning of a butterfly wing. This allows the engrailed gene to function both early in embryo development and then later as a master mimicry switch gene by changing the colour and shape of the butterflies wing.

Read more at:

Continuation of first link posted...

Oct 31, 2014
To their surprise, only one, doublesex, showed an association. Well established as a gene that controls sexual differentiation in insects, doublesex functions through alternative splicing. When copied into messenger RNA, it is cut and rearranged into different isoforms, which then go on to instruct cells whether they should be male or female.

Kronforst and his team found that doublesex is also alternatively spliced into multiple isoforms in Papilio polytes. Two in particular were expressed at extremely high levels in the wings of mimetic butterflies when compared to non-mimetic females. Tracing the doublesex protein from caterpillar to chrysalis to butterfly, the team found expression of doublesex overlaps exactly with wing pattern.

Read more at:

Oct 31, 2014
And finally a suspected clincher:

How one gene controls so many different functions remains unclear. Kronforst suggests that noncoding, regulatory DNA that controls when and where doublesex is expressed may play a role. The team also found that in mimetic butterflies, the doublesex gene is inverted on the genome. This inversion eliminates the possibility of recombination—alleles will remain distinct from each other and accumulate differing mutations. This has led to structural differences in the doublesex protein between mimetic and non-mimetic butterflies. Because doublesex is a transcription factor and activates other genes, the researchers believe these differences may also contribute to wing pattern variation.

Read more at:

Your welcome. Score one for these research teams.

Oct 31, 2014
Search Results for: RNA-mediated Number of Results: 128

Who's keeping score? If it's russell_russell, why do I still have a one star rating when he has 5 stars.

Since our 1996 Hormones and Behavior review, I've detailed every known aspect of RNA-directed DNA methylation, which leads to the amino acid substitutions that differentiate all cell types in all individuals of all species. There's even a model for that -- with examples across species.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

Is it possible that no points are awarded for refutations of pseudoscientific nonsense linked to theories about mutations and/or natural selection lead to the evolution of biodiversity?

Search Results for: mimic
Number of Results: 14
See also: http://perfumingt...bmit.y=0

Nov 03, 2014
Neither concessional nor consolatory is the following:
You are absolutely correct: mutations are not the main drivers of evolution, biodiversity or cell differentiation.
The main drivers, inverted or not, are DNA isoforms. There models for this.
Without scoring at all.

Nov 03, 2014

In the current extant literature, who still refers to mRNAs as DNA isoforms?

What models link the DNA isoforms / mRNAs to cell type differentiation in species from microbes to man via conserved molecular mechanisms?

http://en.wikiped..._isoform Gene isoform "Gene isoforms are mRNAs that are produced from the same locus but are different in their transcription start sites (TSSs), protein coding DNA sequences (CDSs) and/or untranslated regions (UTRs), potentially altering gene function."

Are there any models of nutrient-dependent pheromone-controlled cell type differentiation that include examples from model organisms, which is what I did?

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