DNA coding

[victorqedu]

Hello.

 

DNA has been mapped and we know that DNA stores the information for all the proteins that are necessary for life.

But how does DNA codes for the shape of a organ or for the amount of cells in the brain?

How does DNA stores the information for when to stop growing?

Can you give some detailed links?

 

Thank you.

 

[Essay]

The DNA probably has more regulatory functions, for those protein-coding genes, than there are protein-coding genes.

 

Google: "Sean B. Carroll" limb shape

 

...to get some general ideas about these processes.

 

Also learn about "quorum sensing" and realize that while science doesn't yet know about how mammalian cells do this (that I know about), our organs and tissues must do something similar to quorum sensing.

Edit: No doubt, Gap Junctions and Tight Junctions are critical. Search gap junction function ...for fun.

 

Then put the two concepts together, realizing that quorum sensing is a genetically-mediated process also, and you can see how everything "senses" where to go and what to be.

 

~?

Edited July 2, 2013 by Essay

[CharonY]

There is quite some knowledge about how tissues grow and organisms develop and it is not related to quorums sensing per se (though the principles have some commonality). Quorum sensing really refers the population density sensing of populations of independent cells (or organisms).

The short version for tissue and organ growth is that the cells produce signaling molecules and by the way cells part slight imbalances are produced. These gradients are responsible to cells to form polarity (as they they will affect cellular regulation in dependence on their concentration). This differential growth again leads to more regulatory changes and the cells start forming in certain ways based on what their surrounding cells "tell" them.

In other words cell differentiation is not hard-coded in the genome (as each cells start with the same genome) but rather is the result of cell-cell signaling and gradients of signaling molecules.

[victorqedu]

So quorum sensing can control only the population growth(how big each organ will be).

And quorum sensing has nothing to do directly with the actual shape of the final product(the hearth by example).

The shape is somehow made by these gradients.

But the formation of the gradients is very unclear for me.

If all cells are are made using the same template then how can they build these complex shapes?

 

What I mean is:

- let's say that in the beginning I have a single cell and I will try to obtain the hearth.

- this cell multiplies by mitosis

- all cells being identical they will signal the same thing to the surrounding cells so I can't see how the gradient will get a custom shape like the hearth

- signals can be different only proportional with the population density

- I can see only a spherical shape

 

It looks like the gradients must be somehow coded in the genes.

Edited July 7, 2013 by victorqedu

[Essay]

So quorum sensing can control only the population growth(how big each organ will be).

And quorum sensing has nothing to do directly with the actual shape of the final product(the hearth by example).

The shape is somehow made by these gradients.

But the formation of the gradients is very unclear for me.

If all cells are are made using the same template then how can they build these complex shapes?

 

What I mean is:

- let's say that in the beginning I have a single cell and I will try to obtain the heart.

- this cell multiplies by mitosis

- all cells being identical they will signal the same thing to the surrounding cells so I can't see how the gradient will get a custom shape like the hearth

- signals can be different only proportional with the population density

- I can see only a spherical shape

 

It looks like the gradients must be somehow coded in the genes.

 

Whoops, I probably shouldn't have mentioned quorum sensing, since it has nothing to do with "organ shape" or any complex-animal processes. It is however, an interesting example of the amazing ability of simple cells, and suggestive of how more complex processes might evolve.

===

You mention that, "signals can be different only proportional with the population density." And if that were true, then your point would seem valid. But signals can be more complex, especially the relative ratios of different chemical gradients:

The gradient provides a "different environment" for each cell (or row/layer of cells); and so sensitive genes can be turned on or off, or their expression rates modified, or even linked with other genes--by the different "signals" that the different environment (gradient) produces.

There are several videos by Sean B. Carroll, which explain this much better.

Try http://seanbcarroll.com/

...or try to find his video lectures of "Endless Forms Most Beautiful" & "The Making of the Fittest," which are two books he has available. I've enjoyed that several times on our public-access cable. PBS probably has "What Darwin Never Knew" available.

===

But ultimately, the different environment of each cell will provide signals to the genes of that cell. Different genes react to different signals, and genes react differently to different levels of a signal--or ratio of signals. Sometimes it is a proportional reaction, or it may be an on/off reaction dependent upon some signal threshold.

There are many different possibilities, and those can be modified depending upon the activity of other genes (which are sensing other signals). Sublime design emerges.

~

Edited July 7, 2013 by Essay

[ewmon]

I would think that organ shape and size involves cell differentiation, cell fate, axis determination, etc.

[Essay]

I would think that organ shape and size involves cell differentiation, cell fate, axis determination, etc.

 

Those are good points too, and probably a better perspective for studying development; but all of those processes depend on the genes being signaled in some way to begin, continue, and finally stop each process.

 

The OP also asked about how the signals cause the DNA to act, so we should mention the chemical binding of signal molecules to the DNA directly; as well as the chemical binding of "signal molecules" to other cellular molecules (which then bind to the DNA as a signal). Or there can be a whole cascade of different signal molecules between the cell wall and the genes in the nucleus, but ultimately some signal must tell a gene how to help the cell act out, "as if it knows," its position and function... within the organ or body.

 

Transcription of the genes is "regulated" by the signaling. The chemical bonding of the signal to the DNA (or to the "coating" molecules of DNA) causes the chromosome to change shape--enough to change how easily transcription of the DNA can occur--either stopping or starting, or speeding or slowing-- regulating the production of proteins.

 

~.

Edited July 7, 2013 by Essay

[CharonY]

There is way more to it In addition to transcriptional we also have translational and post translational control. However this is generally true for all regulatory elements and is not limited not to cell differentiation. Although it is involved in it, of course.

 

Suffice to say that no quick summary would do the complexity of the issue justice.And if more details are needed a textbook is going to be a much more valuable source of information.

[Tridimity]

Hi victorqedu,

 

The crux of the question you pose is really one for the field of developmental biology. It is fascinating to contemplate how the genomic DNA present in the zygote following fusion of the gametes - invisible to the naked eye - contains all of the instructions required to specify the development of the organism, including organ size and shape. The genomic DNA present within each cell of the body is identical (excepting sporadic mutations and epigenetic profiles); the difference is that different cell-types have their own unique spatiotemporal gene expression profiles. Drosophila embryogenesis provides an example of the mechanisms by which differences in gene expression can arise. Differences in gene expression are initiated by asymmetries in the distribution of maternal mRNA present in a gradient in the oocyte:

 

http://en.wikipedia.org/wiki/Drosophila_embryogenesis

 

Maternal effect genes mediate specification of the anterior-posterior axis patterning. The maternal effect gene products, in turn, determine the expression patterns of gap genes. Gap genes and pair rule genes then regulate Hox genes, which are critical in determining organ size and shape (1):

 

http://en.wikipedia.org/wiki/Hox_genes

 

The developmental mechanisms that regulate the relative size and shape of organs have remained obscure despite almost a century of interest in the problem and the fact that changes in relative size represent the dominant mode of evolutionary change. Here, I investigate how the Hox gene Ultrabithorax (Ubx) instructs the legs on the third thoracic segment of Drosophila melanogaster to develop with a different size and shape from the legs on the second thoracic segment. Through loss-of-function and gain-of-function experiments, I demonstrate that different segments of the leg, the femur and the first tarsal segment, and even different regions of the femur, regulate their size in response to Ubx expression through qualitatively different mechanisms. In some regions, Ubx acts autonomously to specify shape and size, whereas in other regions, Ubx influences size through nonautonomous mechanisms. Loss of Ubx autonomously reduces cell size in the T3 femur, but this reduction seems to be partially compensated by an increase in cell numbers, so that it is unclear what effect cell size and number directly have on femur size. Loss of Ubx has both autonomous and nonautonomous effects on cell number in different regions of the basitarsus, but again there is not a strong correlation between cell size or number and organ size. Total organ size appears to be regulated through mechanisms that operate at the level of the entire leg segment (femur or basitarsus) relatively independently of the behavior of individual subpopulations of cells within the segment.

 

 

See also this open access PLOS paper on how genes interact to control flower shape in the Snapdragon (2):

 

The development of organs with particular shapes, like wings or flowers, depends on regional activity of transcription factors and signalling molecules. However, the mechanisms that link these molecular activities to the morphogenetic events underlying shape are poorly understood. Here we describe a combination of experimental and computational approaches that address this problem, applying them to a group of genes controlling flower shape in the Snapdragon (Antirrhinum). Four transcription factors are known to play a key role in the control of floral shape and asymmetry in Snapdragon. We use quantitative shape analysis of mutants for these factors to define principal components underlying flower shape variation. We show that each transcription factor has a specific effect on the shape and size of regions within the flower, shifting the position of the flower in shape space. These shifts are further analysed by generating double mutants and lines that express some of the genes ectopically. By integrating these observations with known gene expression patterns and interactions, we arrive at a combinatorial scheme for how regional effects on shape are genetically controlled. We evaluate our scheme by incorporating the proposed interactions into a generative model, where the developing flower is treated as a material sheet that grows according to how genes modify local polarities and growth rates. The petal shapes generated by the model show a good quantitative match with those observed experimentally for each petal in numerous genotypes, thus validating the hypothesised scheme. This article therefore shows how complex shapes can be accounted for by combinatorial effects of transcription factors on regional growth properties. This finding has implications not only for how shapes develop but also for how they may have evolved through tinkering with transcription factors and their targets.

 

 

Organ size and shape is, of course, determined by the number of cells within the organ and their spatial interactions with one another and with their surrounding extracellular matrix (ECM). Cell number is determined by the rates of cell proliferation and death (by necrosis or by the programme of apoptosis). Progression through the cell cycle including commitment to entry into somatic cell division, or mitosis, is intricately regulated by molecular signalling pathways - key components of which are the cyclins and cyclin-dependent kinases (CDKs):

 

http://en.wikipedia.org/wiki/Cell_cycle

 

http://en.wikipedia.org/wiki/Cyclin_dependent_kinase

 

Contact inhibition illustrates the way in which cells typically temper their proliferation in response to their immediate neighbours:

 

http://en.wikipedia.org/wiki/Contact_inhibition

 

Cells will eventually become quiescent (replicative senescence) which usually mirrors the stage of cellular differentiation. Stem cells retain the capacity to proliferate.

 

Apoptosis is similarly regulated by networks of signalling pathways:

 

http://en.wikipedia.org/wiki/Apoptosis

 

All of these processes act in concert to determine the overall size and shape and organs.

 

Best wishes,

 

Tridimity

 

 

Ref.

 

1. Stem DL (2000) The Hox gene Ultrabithorax modulates the shape and size of the third leg of Drosophila by influencing diverse mechanisms. Dev Biol 256 (2): 355-66

2. Cui M, Copsey L, Green AA, Bangham JA & Coen E (2010) Quantitative Control of Organ Shape by Combinatorial Gene Activity. PLoS Biol 8(11): e1000538 doi:10.1371/journal.pbio.1000538