Genetic Toolkits and Multicellularity

[rwenzori]

Actually a very good point.

I seem to remember reading that the figure is over 99.9%. It's a very telling point, and very difficult to build into a creationist view. God must be amazingly weak to have to create his chosen creature purposefully via a gazillion years of very iffy evolutionary processes. If he/she/it/whatever were all powerful - just create what you want onetime.

 

[alloytoo]

I seem to remember reading that the figure is over 99.9%. It's a very telling point, and very difficult to build into a creationist view. God must be amazingly weak to have to create his chosen creature purposefully via a gazillion years of very iffy evolutionary processes. If he/she/it/whatever were all powerful - just create what you want onetime.

Well we could just be a glorified petri dish, allowed to "simmer" at the back of the lab.......

......some time in the distant future.......

The joyous dancing of the faithful subsided, scientists began to dejectedly dismantle their research projects, and publishers abandoned a project to print a Millenium edition of "Origin of the species"

God, graciously acceded to requests to appear on new (very very New) Prime time television show "God is with us."

On the day God declined makeup, he appeared somewhat uncomfortable at the host's genuflections and won oohs and aahs as he insisted they sit alongside him on the couch.

Some thought his smile seemed strained, and that he appeared to shift nervously during the praise and worship segment, but their opinions as dirty former athiests didn't count for much anyway.

At last the show came to the meat of the matter, the host, a rotound twice devorced televangelist with serious tax problems leant forward to ask the ultimate question.

An unruely segment of the crowed started chanting "42", "42" but they were soon quashed.

"God, almighty and most praised." he began.

"Call me Joe." God said.

Unpeturbed the host continued. "Oh lord." He entoned. "What is the purpose of our lives?"

The crowd began to murmur 'purpose' and god looked uncomfortable as the murmur rose to a chant.

"er....well"

"What were we put here to do."

"Put here to do!" the crowd chanted, "Put here to do!"

God cleared his throat. "There's no purpose, none really."

In the silence somebody dropped a pin.

God continued, "You lot just happened really."

"But..." the host looked around for direction. "You created us."

The crowd quickly adopted this new mantra:

"You created us!"

"You created us!"

God appeared to be blushing, he stood nerviously eying the exit...."It was all really just poor housekeeping. A few toots after work, a glass left behind, a few eons and you lot just evolved......."

 

[rwenzori]

Well we could just be a glorified petri dish, allowed to "simmer" at the back of the lab.......

60 Minutes: Do you chuckle when you hear people say you are God?

EC: Oh It's nonsense.

Disillusionment is setting in.....

 

[Phronesis]

No not even that complicated yet(although that makes it even more obvious how much we assume), simple mass interactions make it complex enough already.

The point I'm so clumsilly trying to make is that if we are unable to accurately determinde the exact chain of events that lead to what we now observe, how can we assume that anything was planned with a purpose, and not simply cause and effect? Because the smallest little change could steer the whole general direction of the chain of events.

Fair enough. However that can cut both ways. Just because we do not know enough about the system also does not imply there is no plan. As to the "smallest change could steer the whole general chain of events". Look at the developmental program. A small change could change the outcome of the developmental program (e.g. drug use could alter development of a fetus), but the general direction and chain of events still result in the formation of a new born (if the process is succesful). The process uses NS and RV as well as environmental cues. While small changes or even big changes might steer the process, the outcome is similar for a variety of environmental changes. The outcome (if successful) is not the same, but similar regardless of environmental cues.

Do we actually know how those genes you spoke about came to be in those primitive creatures? Do we know for a fact that it only led to the hedgehog? Why a hedgehog? They haven't really changed the course of history for the better(I'm assuming of course ).

The origin of the genes (whether agency or mindless processes) is not important. Just how they biased evolutionary pathways. I was talking about the hedgehog gene . The reason for the name of this gene is that a malfunctioning hh gene often results in the formation of small pointy projections on embryos, similar to that on hedgehogs.

And if gene development has a purpose, why did the Dodo evolve in the first place? Or the other 90% of creatures ever born only to find themselves extinct a while later.

Are you implying that it is a bad design?
This looks like the old argument from bad design again (what alloytoo and rwenzori are trying to do here). What is the origin of design, regardless of whether it is good or bad?
I am curious, are you intentionally developing a theodicy based on your perception of bad design? Remember, the development of a theodicy is for those who believe in a necessary mind .

 

[Geriatrix]

Fair enough. However that can cut both ways. Just because we do not know enough about the system also does not imply there is no plan. As to the "smallest change could steer the whole general chain of events". Look at the developmental program. A small change could change the outcome of the developmental program (e.g. drug use could alter development of a fetus), but the general direction and chain of events still result in the formation of a new born (if the process is succesful). The process uses NS and RV as well as environmental cues. While small changes or even big changes might steer the process, the outcome is similar for a variety of environmental changes. The outcome (if successful) is not the same, but similar regardless of environmental cues.

I see what you're saying. I guess we're just looking at the same apple from two points of view then.

The origin of the genes (whether agency or mindless processes) is not important. Just how they biased evolutionary pathways. I was talking about the hedgehog gene . The reason for the name of this gene is that a malfunctioning hh gene often results in the formation of small pointy projections on embryos, similar to that on hedgehogs.

Hehehe, my bad. So what does the gene do when its not malfunctioning?

Are you implying that it is a bad design?
This looks like the old argument from bad design again (what alloytoo and rwenzori are trying to do here). What is the origin of design, regardless of whether it is good or bad?
I am curious, are you intentionally developing a theodicy based on your perception of bad design? Remember, the development of a theodicy is for those who believe in a necessary mind .

No I'm implying no design. I'm implying no purpose. Except if you want to see it.

 

[Phronesis]

Hehehe, my bad. So what does the gene do when its not malfunctioning?

From the OP:

The hedgehog signaling pathway plays a fundamental role in cell pattrerning, cell proliferation and participates in the development of tissues and organs during the stages of animal development. It exerts its effect by influencing the transcription of many target genes in a concentration dependent manner.

Hedgehog proteins are the only examples of sterolation in contempory biology.

 

[Phronesis]

A few interesting observations:

1) Components of the multicellular signaling pathway (sonic-hedgehog) were present in ancestral lineages way before the emergence of multi-cellularity.

2) The origin of multi-cellular body plans roughly coincide with an increase in atmospheric oxygen pressure as well as the first bona fide hedgling.

3) Hedglings are the only examples of post-translational sterolation (addition of cholesterol) of proteins in contempory biology and oxygen is needed for cholesterol synthesis, more importantly, oxygen is needed for placing the hydroxyl group in the 3-position of cholesterol which plays a crucial role in subsequent transformations (including sterolation).

4) While large parts of the hedgehog-signaling pathway was present, a little extra oxygen was needed to unlock multicellular signaling capabilities of hedglings.

5) The increase in atmospheric oxygen was bought on about by life itself and this increase in atmospheric oxygen in turn seemed to have unlocked the pathways to multicellular body plans

And now this:
Oxygen Key To 'Cut And Paste' Of Genes

ScienceDaily (July 12, 2009) — An oxygen-sensitive enzyme has been found to play a key role in how genes create the many different proteins that make up our bodies.

The finding shows that the enzyme, termed Jmjd6, directly intervenes in the process in which the DNA of our genes is ‘cut and pasted’ into instructions for the creation of specific proteins.

The discovery, reported in this week’s Science by a team led by scientists from Oxford University and Ludwig-Maximilians-University, Munich, opens up a new area of molecular research into conditions such as heart disease and cancer.

‘Previous work from Oxford has shown that some of these enzymes, called oxygenases, affect which genes are expressed in response to low levels of oxygen. What we have now found is that they also regulate the specific form this expression takes – to give the different proteins that make up everything from heart cells to tumours,’ said Professor Chris Schofield of Oxford University’s Department of Chemistry, one of the authors of the paper.

Genes, stored in the form of DNA, are converted into proteins by a ‘middleman molecule’ called Messenger Ribonucleic Acid – or ‘mRNA’.

Individual genes can often give rise to many different proteins because of a process known as mRNA splicing which enables the cutting and pasting of the mRNA that is produced from DNA. The proteins that the new oxygenase, termed Jmjd6, acts on are involved in regulating the 'cutting and pasting' process.

Angelika Böttger, who led the Munich group, said: ‘The discovery of a role for an oxygenase in mRNA splicing reveals that it is very likely that oxygen levels are involved in regulating almost all steps in the process of gene expression. The challenge now is to determine how the pattern of genes changes in different environments when oxygen is in short supply, enabling us to tackle important questions such as "why do tumour cells respond differently to low oxygen levels than normal cells?"'

A little more about the protein:

This gene encodes a nuclear protein with a JmjC domain. JmjC domain-containing proteins are predicted to function as protein hydroxylases or histone demethylases. This protein was first identified as a putative phosphatidylserine receptor involved in phagocytosis of apoptotic cells; however, subsequent studies have indicated that it does not directly function in the clearance of apoptotic cells, and questioned whether it is a true phosphatidylserine receptor. Multiple transcript variants encoding different isoforms have been found for this gene.

Present where? Well, all over it seems, even proteobacteria (one of the most primitive groups of organisms:
http://www.ebi.ac.uk/interpro/IEntry?ac=IPR003347

 

[Phronesis]

From the opening post;
Therefore, words like "pre-existing", "latent" and "potential" seem apt in describing the hedghog signaling pathway and the unfolding of multicellular body plans in relation to the increase in atmospheric oxygen pressure. "Innovation" perhaps not so much, seeing that only real innovation was bought on about by life itself namely the increase in atmospheric oxygen. This increase in atmospheric oxygen in turn seemed to have unlocked the pathways to multicellular body plans (>3 cell types).

A new article strenghtens this view of evolution whereby pre-existing pathways unfold into their potential roles in the emergence of multicellular body plans, thereby biasing evolutionary trajectories towards a few ends.
The Hedgehog Signaling Pathway: Where Did It Come From?

Figure 3. A parsimonious scenario for the evolution of the Ptc/Smo system.
We hypothesize that during the transition to multicellularity, a pre-existing lipid homeostasis system took on a new function in signaling. Initially, an ancient lipid transporter diversified; one of its descendents came under the transcriptional control of a GPCR that sensed the same lipid (i.e., forming a negative homeostatic feedback loop). Then, the fortuitous addition of a protein moiety to the lipid in question brought the system under the control of gene expression; a neighboring cell could now secrete the lipid at will (by coupling it to the protein moiety). Because the combined lipid–protein molecule would block the transporter, this meant that the sending cell was capable of changing the perceived homeostatic state of the receiving cell, which would have established a graded (quantitative) mode of cell–cell communication.​

Also:

Figure 4: Origins of the parts in the hedgehog signaling pathway. (Red = absent, Orange = reasonable sequence and/or structural simlarity, Green = present, Graded green = part of the same family, Brown = unsure.).​

Bigger pic here.

Note that many of the components of the signaling pathway are present in various bacterial and archaeal lineages. Also note that the origin of multicellular body plans roughly coincide with an increase in atmospheric oxygen pressure as well as the first bona fide hedgling. Remember, hedglings are the only examples of post-translational sterolation (addition of cholesterol) of proteins in contempory biology. Why is this interesting? Well, oxygen is needed for cholesterol synthesis, more importantly, oxygen is needed for placing the hydroxyl group in the 3-position of cholesterol which plays a crucial role in subsequent transformations (including sterolation). Thus, while large parts of the hh-signaling pathway was present, a little extra oxygen was needed to unlock multicellular signaling capabilities of hedglings.

And now note information from the above article:

Complex body plans require sophisticated cell–cell signaling pathways. How these pathways evolved is often not very well understood. Here, we argue that the Hedgehog (Hh) signaling pathway may have arisen from systems that were originally designed for the transport and homeostasis of certain bacterial sterol analogs—the hopanoids.

We assume that the original function of Ptc was simply to transport an unwanted lipid molecule out of the cell. Smo, on the other hand, derives from a protein family whose main function is to sense and to transduce extracellular signals (i.e., the GPCR family). Therefore, we propose the following scenario: let us imagine that, in primitive eukaryotes, Smo was initially a receptor sensing lipid molecules and was acting upstream of the primitive Ptc transporter (Figure 3). The two molecules would have formed a simple homeostasis system; Smo would sense the abundance of a certain lipid and would transcriptionally induce Ptc whenever this lipid was in excess and needed to be removed from the membrane (i.e., pumped away). We propose that when multicellular organisms arose, this system was available and was recruited for a new purpose: cell-to-cell signaling.

The intriguing homology between components of lipid homeostasis pathways and components of the Hh signaling pathway leads to the hypothesis that the central membrane–players of the Hh signaling cascade—Smo and Ptc—evolved from a pre-existing lipid-sensing/homeostasis pathway. We propose a model of simple evolutionary steps, which posits that Ptc acts by pumping an activator of Smo, rather than an inhibitor. This scenario is compatible with most experimental data so far. The step-wise construction of pathways from older, pre-existing modules is turning out to be a general theme in developmental biology [24].

The similarities between evolution and development are striking indeed.... biased towards a few endpoints through random variation and selection.
And articles to show how and why:
1) Parallels between evolution and development:
Getting beyond the population genetics/developmental biology split: A New Evolutionary Synthesis

2) A few endpoints (small subset, limited variation) out of all the possible endpoints:
An End to Endless Forms: Epistasis, Phenotype Distribution Bias, and Nonuniform Evolution

3) Evolution learns:
Facilitated Variation: How Evolution Learns from Past Environments To Generalize to New Environments

4) And proteins control evolution:
Evolution's new wrinkle: Proteins with cruise control provide new perspective

 

[Phronesis]

Evolution "learns", and development as well...

Cells in developing tissue consider their history of signaling exposure to determine location

Pasadena, Calif.—Researchers at the California Institute of Technology (Caltech) have proposed a novel model that differs from a widely held hypothesis about the mechanisms by which developing animals pattern their tissues and structures.

Cells in a developing animal require information about their position with respect to other cells so that they can adopt specific patterns of gene expression and function correctly. The most accepted paradigm is that this positional information comes in the form of chemical signals called morphogens; morphogens are differentially distributed across the developing field, with cells acquiring the information about their position relative to their neighbors by "measuring" and interpreting the local concentrations of the morphogen.

Despite the identification of several families of morphogens in many organisms, the hypothesis that cells differentially respond to morphogen concentrations generally hasn't been directly tested.

The Caltech researchers, led by assistant professor of biology Angelike Stathopoulos, used an approach that combines mathematical modeling and developmental genetics experiments to examine the mechanisms underlying patterning of the developing wing in the fruit fly, Drosophila melanogaster. They found that cells cannot adopt multiple patterns of gene expression solely by measuring the local concentration of a morphogen.

"During metamorphosis, imaginal disc tissues need to form structures that contribute to the adult body plan," explains Stathopoulos. Imaginal discs are parts of the insect larva that will become structures that contribute to the adult body plan. "This imaginal disc tissue is plastic, in that the cells are still making decisions about what part of the organ they should develop into. A decision has been made that these cells must make 'body part X,' but how do they determine whether to make the proximal or distal portion, or decide which is facing up or down? This is where morphogens come in."

In fruit flies, a regulatory molecule called Hedgehog provides such information, along the anterior-posterior axis (from base to tip) of the developing wing. For the wing to properly form, cells along this axis need to "act" by turning on the Hedgehog signaling pathway, although not all of the cells do so, Stathopoulos says.

"We found that in the developing wing of the fruit fly, cells do not acquire positional information by only measuring the concentration of the Hedgehog morphogen at a given time, but instead require information about their history of exposure," says Marcos Nahmad, a graduate student in control and dynamical systems at Caltech, jointly supervised by Stathopoulos and John Doyle, the John G. Braun Professor of Control and Dynamical Systems, Electrical Engineering, and Bioengineering. Nahmad is the first author of a paper about the research, coauthored by Stathopoulos, that appears in the September 29 issue of the open-access online journal PLoS Biology.

In their experiments, the researchers found evidence that certain cells receive the Hedgehog signal only for a short period of time, and this transient exposure causes them to adopt a gene expression pattern that is different from that of other cells that receive the Hedgehog signal constantly, and from those that never received it at all.

In a sense, says Stathopoulos, the cells are able to "remember" that they've been exposed to the morphogen. "What I mean is they remember having 'seen' a morphogen concentration that activates a signal within them. Even if the concentration of the morphogen decreases subsequently, cells still retain the ability to activate the pathway."

"An exciting outcome of our model is that the ability of cells to respond to the history of morphogen exposure is wired in the gene network architecture that controls patterning of the developing wing. As the Hedgehog pathway architecture is widely conserved from flies to humans, this mechanism of patterning may explain how cells in other developing systems acquire positional information," Nahmad says.

"As developmental biologists, we want to understand how the body plan is specified, and how different animals exhibit different shapes and patterns. What we've shown here is that it's important to consider the temporal sequences of events," Stathopoulos says.

"The dynamics of the system are instructional. In the past, for the most part, this has been ignored, because it's just too complicated. People have formulated models by looking at the endpoint. We believe that even more insights into patterning have likely been missed for this reason," she adds.

###
The work in the paper, "Dynamic Interpretation of Hedgehog Signaling in the Drosophila Wing Disc," was funded by the National Institutes of Health and the Searle Scholar Program.

Hedgehog signaling components were present in ancestral lineages way before the emergence of multi-cellularity.

 

[Phronesis]

How is this for an interting observation:

"Those are the things that not even the simplest organism can do without and that have remained untouched by millions of years of evolution -- the bare essentials of life".

From here:
First-Ever Blueprint of 'Minimal Cell' Is More Complex Than Expected

ScienceDaily (Nov. 27, 2009) — What are the bare essentials of life, the indispensable ingredients required to produce a cell that can survive on its own? Can we describe the molecular anatomy of a cell, and understand how an entire organism functions as a system? These are just some of the questions that scientists in a partnership between the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and the Centre de Regulacio Genòmica (CRG) in Barcelona, Spain, set out to address.

This image represents the integration of genomic, metabolic, proteomic, structural and cellular information about Mycoplasma pnemoniae in this project: one layer of an Electron Tomography scan of a bottle-shaped M. pneumoniae cell (grey) is overlaid with a schematic representation of this bacterium's metabolism, comprising 189 enzymatic reactions, where blue indicates interactions between proteins encoded in genes from the same functional unit. Apart from these expected interactions, the scientists found that, surprisingly, many proteins are multifunctional. For instance, there were various unexpected physical interactions (yellow lines) between proteins and the subunits that form the ribosome, which is depicted as an Electron microscopy image (yellow). (Credit: Takuji Yamada /EMBL)​

In three papers published back-to-back in Science, they provide the first comprehensive picture of a minimal cell, based on an extensive quantitative study of the biology of the bacterium that causes atypical pneumonia, Mycoplasma pneumoniae. The study uncovers fascinating novelties relevant to bacterial biology and shows that even the simplest of cells is more complex than expected.

Mycoplasma pneumoniae is a small, single-cell bacterium that causes atypical pneumonia in humans. It is also one of the smallest prokaryotes -- organisms whose cells have no nucleus -- that don't depend on a host's cellular machinery to reproduce. This is why the six research groups which set out to characterize a minimal cell in a project headed by scientists Peer Bork, Anne-Claude Gavin and Luis Serrano chose M. pneumoniae as a model: it is complex enough to survive on its own, but small and, theoretically, simple enough to represent a minimal cell -- and to enable a global analysis.

A network of research groups at EMBL's Structural and Computational Biology Unit and CRG's EMBL-CRG Systems Biology Partnership Unit approached the bacterium at three different levels. One team of scientists described M. pneumoniae's transcriptome, identifying all the RNA molecules, or transcripts, produced from its DNA, under various environmental conditions. Another defined all the metabolic reactions that occurred in it, collectively known as its metabolome, under the same conditions. A third team identified every multi-protein complex the bacterium produced, thus characterising its proteome organisation.

"At all three levels, we found M. pneumoniae was more complex than we expected," says Luis Serrano, co-initiator of the project at EMBL and now head of the Systems Biology Department at CRG.

When studying both its proteome and its metabolome, the scientists found many molecules were multifunctional, with metabolic enzymes catalyzing multiple reactions, and other proteins each taking part in more than one protein complex. They also found that M. pneumoniae couples biological processes in space and time, with the pieces of cellular machinery involved in two consecutive steps in a biological process often being assembled together.

Remarkably, the regulation of this bacterium's transcriptome is much more similar to that of eukaryotes -- organisms whose cells have a nucleus -- than previously thought. As in eukaryotes, a large proportion of the transcripts produced from M. pneumoniae's DNA are not translated into proteins. And although its genes are arranged in groups as is typical of bacteria, M. pneumoniae doesn't always transcribe all the genes in a group together, but can selectively express or repress individual genes within each group.

Unlike that of other, larger, bacteria, M. pneumoniae's metabolism doesn't appear to be geared towards multiplying as quickly as possible, perhaps because of its pathogenic lifestyle. Another surprise was the fact that, although it has a very small genome, this bacterium is incredibly flexible and readily adjusts its metabolism to drastic changes in environmental conditions. This adaptability and its underlying regulatory mechanisms mean M. pneumoniae has the potential to evolve quickly, and all the above are features it also shares with other, more evolved organisms.

"The key lies in these shared features," explains Anne-Claude Gavin, an EMBL group leader who headed the study of the bacterium's proteome: "Those are the things that not even the simplest organism can do without and that have remained untouched by millions of years of evolution -- the bare essentials of life".

This study required a wide range of expertise, to understand M. pneumoniae's molecular organisation at such different scales and integrate all the resulting information into a comprehensive picture of how the whole organism functions as a system -- an approach called systems biology.

"Within EMBL's Structural and Computational Biology Unit we have a unique combination of methods, and we pooled them all together for this project," says Peer Bork, joint head of the unit, co-initiator of the project, and responsible for the computational analysis. "In partnership with the CRG group we thus could build a complete overall picture based on detailed studies at very different levels." Bork was recently awarded the Royal Society and Académie des Sciences Microsoft Award for the advancement of science using computational methods. Serrano was recently awarded a European Research Council Senior grant.

More complex than expected Can anyone say biased/front-loaded evolution?

 

[Phronesis]

Sonic hedgehog... still playing, still surprising:
Sonic Hedgehog Gene Found in an Unexpected Place During Limb Development

ScienceDaily (Mar. 10, 2010) — Sonic hedgehog, a gene that plays a crucial rule in the positioning and growth of limbs, fingers and toes, has been confirmed in an unexpected place in the embryos of developing mice -- the layer of cells that creates the skin.

Named for a video game character, Sonic hedgehog describes both a gene and the protein it produces in the body. Its study is important to increase understanding of human birth defects.

It was thought to be exclusively present in the cell layer that builds bone and muscle, called the mesoderm. But University of Florida Genetics Institute researchers have discovered that Sonic hedgehog is also at work in mice limb buds in what is known as the ectoderm, the cell layer that gives rise to the skin in vertebrates.

Finding Sonic hedgehog in this layer of cells is loosely akin to discovering that yeast has crept from the batter to the frosting, where it has the surprising effect of limiting how much the cake will rise. More literally, instead of causing appendages to grow, Sonic hedgehog seems to act as a failsafe mechanism to keep additional digits from developing.

"Sonic hedgehog protein determines how your limbs form, and why your pinky is at the bottom of your hand and your thumb is at the top," said Brian D. Harfe, an associate professor of molecular genetics and microbiology at the UF College of Medicine. "But what's been previously published is only part of the picture. We determined that Sonic hedgehog signaling is required in the ectoderm to have normal digit formation. Get rid of it, and an extra digit forms."

In this case, when scientists disrupted Sonic hedgehog signaling in a small region of the limb buds of embryonic mice, an additional digit began to arise in what would be the mouse paw.

The discovery, recently published in the Proceedings of the National Academy of Sciences, suggests that Sonic hedgehog's role in the growth of appendages is far more complex than originally thought. Developmental biologists may have to rethink established theories about how limbs are patterned in vertebrates -- an effort that could provide insight into human birth defects.

"We used technology where a viral protein seeks out specific sequences of DNA," said Cortney M. Bouldin, a graduate student in the Interdisciplinary Program in Biomedical Sciences in the department of molecular genetics and microbiology. "We concentrated on disabling a protein essential for Sonic hedgehog signaling. Although it has been removed from the limb before, we wanted to specifically remove it from the ectoderm. When we did that, in the latter stages of development, we saw extra cartilage and the early beginnings of another digit."

Sonic hedgehog signaling in the ectoderm of limb buds may act as a buffering system that prevents unneeded growth, Bouldin said.

The UF research was sparked by studies of gene activity in the limb buds of mice by William J. Scott, a professor of pediatrics at the University of Cincinnati. Scott used a microarray experiment to examine gene expression levels in the ectoderm of mice limb buds, finding activity that could not be possible without the presence of Sonic hedgehog.

UF researchers were able to advance this investigation from cell studies to developing mice embryos by knocking out gene expression in a small region of the ectodermal layer. It allowed them to observe early limb development in the absence of Sonic hedgehog signaling.

"The view had been if you reduce signaling, if anything you would get fewer fingers," said Scott, who did not participate in the UF research. "We now know we can't disregard Sonic hedgehog signaling in the ectoderm. It still has its predominant effect in the tissue where it is made, but it does something more than we thought it did previously. When we try to understand problems that arise with limb growth in humans, we will be able to examine those possibilities."

Harfe said the next phase of the work will be to observe what happens when Sonic hedgehog signaling is disrupted through larger segments of the ectodermal layer. Ultimately, researchers hope the work will lead to quality of life improvements for people.

"We would like to repair limb defects in humans and enhance regeneration of limbs, helping people who might cut off fingers in an accident, for example," Harfe said.

The work was funded by the UF College of Medicine.

So now you know why some organisms have five digits.... a protein named after computer game character.
Many of the components of the signaling pathway were present waaaaay before the emergence of multicellular organisms, even present in various bacterial and archaeal lineages.