Molecular Development: Difference between revisions

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==Deoxyribonucleic acid==
==Deoxyribonucleic acid==
(DNA)
Deoxyribonucleic acid (DNA) consists of 4 nucleotides:
 
* Adenine (A)
* A Adenine
* Cytosine (C)
* C Cytosine
* Guanine (G)
* G Guanine
* Thymine (T)
* T Thymine




==Ribonucleic acid==
==Ribonucleic acid==
(RNA)
Ribonucleic acid (RNA) consists of 4 nucleotides:


* A Adenine
* Adenine (A)
* C Cytosine
* Cytosine (C)
* G Guanine
* Guanine (G)
* U Uracil
* Uracil (U)
|}


The original "RNA family" consisted of just 3 main members; transfer RNA (tRNA), ribosomal RNA (rRNA) and messenger RNAs (mRNA). Involved in gene expression through protein translation (synthesis).  
The original "RNA family" consisted of just 3 main members; transfer RNA (tRNA), ribosomal RNA (rRNA) and messenger RNAs (mRNA). Involved in gene expression through protein translation (synthesis).  
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| piwi-associated RNA || piRNA || short regulatory RNA || Example
| piwi-associated RNA || piRNA || short regulatory RNA || Example
|-
|-
| long non-coding RNA || ncRNA || non-coding RNA greater than 200bp in length suggested to have many different roles in signalling, protein processing and differentiation|| Example
| long non-coding RNA || ncRNA || non-coding RNA greater than 200bp in length may have different roles in signalling, protein processing and differentiation || Example
|}
|}


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Hedgehog signaling pathway<ref><pubmed>19040769</pubmed>| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614485 PMC2614485] | [http://genomebiology.com/content/9/11/241 Genome Biology]</ref>
Hedgehog signaling pathway<ref><pubmed>19040769</pubmed>| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614485 PMC2614485] | [http://genomebiology.com/content/9/11/241 Genome Biology]</ref>


Note spelling difference: USA signaling, UK signalling.


{{Factor Links}}
{{Factor Links}}
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Embryo left-right asymmetry pathway<ref><pubmed>23256866</pubmed>| [http://www.biomedcentral.com/1741-7007/10/102 BMC Biology]</ref>
Embryo left-right asymmetry pathway<ref><pubmed>23256866</pubmed>| [http://www.biomedcentral.com/1741-7007/10/102 BMC Biology]</ref>


:Links: [[Axis Formation]]
The mechanisms that specify location within the embryo, therefore establishing axes, appears to be controlled by similar signaling mechanisms in different species.
 
 
:'''Links:''' [[Developmental Mechanism - Axes Formation|Axis Formation]]
==Epigenetics==
==Epigenetics==
{|
{|

Revision as of 11:42, 15 September 2014

Embryology - 28 Mar 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
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Introduction

Amphibian oocyte transcription
Epigenetics mechanisms[1]

This page is a link to many different resources related to molecular development. I am 2.85 billion nucleotides of DNA, but so is a chimpanzee, and all this DNA encodes only about 20,000-25,000 protein-coding genes. In development, I am not that different from a mouse or a fly and many of the signals that regulate development are used time and time again.

We have come a long way from just observing development to now wanting to understand how the complex program of development is controlled. Using new research tools and some excellent animal models researchers have discovered common themes and mechanisms that tie all embryonic development together.

What is remarkable, given our biological diversity, is the strong evolutionary conservation of developmental mechanisms. This has been a boon in allowing the use of many (easier) model systems such as the genetist's tool the fruitfly, and the worm, frog, chicken, zebrafish and mouse (see other embryos page).

A continuing theme also seems to be the reuse of signals at different times and places within the embryo, for diiferent jobs. This has given rise to the concept of "switches" which by themselves may contain no "information" but to activate other genes or switches. Finally, you can imagine that of our 20,000-25,000 protein-coding genes, a large number of these may only be expressed during development or if reused, have a completely different role in the mature animal.

In terms of molecular mechanisms, the field of epigenetics has begun to florish with some recent important findings.

Molecular mechanisms of development is an exciting area and requires a variety of different skills. This page introduces only a few examples and should give you a feel for the topic. Note that each section of system notes has a page covering molecular development in that system. I have included information about the basic building blocks of proteins (amino acids).


Molecular Links: molecular | genetics | epigenetics | mitosis | meiosis | X Inactivation | Signaling | Factors | Mouse Knockout | microRNA | Mechanisms | Developmental Enhancers | Protein | Genetic Abnormal | Category:Molecular


Hox Genes
Fly wild-type head.jpg Fly antennapedia head.jpg
Fly wild-type head[2] Fly antennapedia mutant head[2]
Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular
Mechanism Links: mitosis | cell migration | cell junctions |epithelial invagination | epithelial mesenchymal transition | mesenchymal epithelial transition | epithelial mesenchymal interaction | morphodynamics | tube formation | apoptosis | autophagy | axes formation | time | molecular


Some Recent Findings

  • The Encyclopedia of DNA Elements (ENCODE) project Wed, Sep 5, 2012 "The Human Genome Project produced an almost complete order of the 3 billion pairs of chemical letters in the DNA that embodies the human genetic code — but little about the way this blueprint works. Now, after a multi-year concerted effort by more than 440 researchers in 32 labs around the world, a more dynamic picture gives the first holistic view of how the human genome actually does its job." NIH Nature
  • Properties of developmental gene regulatory networks[3] Introductory paper from the "Gene Networks in Development and Evolution Special Feature Sackler Colloquium" (2008) "The modular components, or subcircuits, of developmental gene regulatory networks (GRNs) execute specific developmental functions, such as the specification of cell identity. We survey examples of such subcircuits and relate their structures to corresponding developmental functions. These relations transcend organisms and genes, as illustrated by the similar structures of the subcircuits controlling the specification of the mesectoderm in the Drosophila embryo and the endomesoderm in the sea urchin, even though the respective subcircuits are composed of nonorthologous regulatory genes."

Starting Out

Model of Sonic hedgehog signaling in the drosophila wing

There are several different ways to begin to look at molecular development.

  • look at the earliest molecular events involved in patterning the differentiation of cells- axis formation.
  • or look at early events in patterning with differentiation and migration of cells to form the trilaminar embryo (gastrulation).
  • or look at the signaling mechanisms and the different types of factors involved.
  • or look at their role in the development of specific systems.

Signaling during development, though complex, can also be grouped into a few specific classes. These mechanisms have also been listed and described briefly on Signaling Mechanisms page.

For this section, Molecular Biology of the Cell (now indexed and available online from PubMed) and the extracted Cell Biology version are good reference texts. Also the key journals in this area are: Development, Genes and Development, PNAS, EMBOJ.

There is also detailed molecular information available from the abnormalities (page 2 of each section of notes) where there are links to the OMIM Database entry for specific genetic disorders.

Please understand that these notes are a new addition and are therefore under constant revision.

Gene Expression

DNA -> RNA -> Protein

Our genetic information is stored within each cell in cell organelles of the nucleus and mitochondria.

  • In the nucleus as chromosomes.
  • In the mitochondria as circular DNA.

Gene expression can often simply be described by the pathway: DNA -> mRNA -> Protein. While each cell contains the same genetic material, not all genes are ever expressed and the subset of genes expressed at any one time affects cellular differentiation and mature cell function. This can be impacted by both signaling and epigenetic mechanisms.

The human chromosomes consist of proteins and nucleic acids, the common nucleic acids or bases that forms DNA can be represented by a standardised IUPAC single letter code.

Deoxyribonucleic acid

Deoxyribonucleic acid (DNA) consists of 4 nucleotides:

  • Adenine (A)
  • Cytosine (C)
  • Guanine (G)
  • Thymine (T)


Ribonucleic acid

Ribonucleic acid (RNA) consists of 4 nucleotides:

  • Adenine (A)
  • Cytosine (C)
  • Guanine (G)
  • Uracil (U)

The original "RNA family" consisted of just 3 main members; transfer RNA (tRNA), ribosomal RNA (rRNA) and messenger RNAs (mRNA). Involved in gene expression through protein translation (synthesis).

In recent years this RNA family, shown in the table below, has been expanded to include newly identified members: small nuclear RNA (snRNA) , small nucleolar RNA (snoRNA), and short regulatory RNA (piwi-associated RNA (piRNA), endogenous short-interfering RNA (endo-siRNA) and microRNA (miRNA) and now long non-coding RNA (lncRNA). Each of these new family members has a range of potential roles in development and differentiation.

RNA Class Acronym Roles Examples
transfer RNA tRNA carry amino acid in cell cytoplasm to ribosome Example
messenger RNA mRNA transcribed from DNA in cell nucleus and relocate to cytoplasm for translation on the ribosome Example
ribosomal RNA rRNA structural RNA that allow the assembly of ribosomal proteins in the cytoplasm into ribosomal subunits required for protein translation Example
small nuclear RNA snRNA involved in cell nucleus RNA splicing Example
small nucleolar RNA snoRNA modify other small RNAs (rRNAs and tRNAs) Example
microRNA miRNA post-transcriptional regulator of gene expression Example
endogenous short-interfering RNA endo-siRNA short regulatory RNA Example
piwi-associated RNA piRNA short regulatory RNA Example
long non-coding RNA ncRNA non-coding RNA greater than 200bp in length may have different roles in signalling, protein processing and differentiation Example

Protein

The individual amino acids that form all proteins can be represented by a standardised single letter code, or three letter code or by their entire name.

Single Letter Code

A - Alanine (Ala) | C - Cysteine (Cys) | D - Aspartic Acid (Asp) | E - Glutamic Acid (Glu) | F - Phenylalanine (Phe) | G - Glycine (Gly) | H - Histidine (His) | I - Isoleucine (Ile) | K - Lysine (Lys) |L - Leucine (Leu) | M - Methionine (Met) | N - Asparagine (Asn) | P - Proline (Pro) | Q - Glutamine (Gln) | R - Arginine (Arg) | S - Serine (Ser) | T - Threonine (Thr) | V - Valine (Val) | W - Tryptophan (Trp) | Y - Tyrosine (Tyr)

Amino Acid 3-Letter 1-Letter Side chain polarity Side chain acidity or basicity of neutral species Hydropathy index

[4]

Alanine Ala A nonpolar neutral 1.8
Arginine Arg R polar basic (strongly) -4.5
Asparagine Asn N polar neutral -3.5
Aspartic acid Asp D polar acidic -3.5
Cysteine Cys C polar neutral 2.5
Glutamic acid Glu E polar acidic -3.5
Glutamine Gln Q polar neutral -3.5
Glycine Gly G nonpolar neutral -0.4
Histidine His H polar basic (weakly) -3.2
Isoleucine Ile I nonpolar neutral 4.5
Leucine Leu L nonpolar neutral 3.8
Lysine Lys K polar basic -3.9
Methionine Met M nonpolar neutral 1.9
Phenylalanine Phe F nonpolar neutral 2.8
Proline Pro P nonpolar neutral -1.6
Serine Ser S polar neutral -0.8
Threonine Thr T polar neutral -0.7
Tryptophan Trp W nonpolar neutral -0.9
Tyrosine Tyr Y polar neutral -1.3
Valine Val V nonpolar neutral 4.2

Hydropathy Index[4]

  • a number representing the hydrophobic or hydrophilic properties of the amino acid sidechain.
  • larger the number the more hydrophobic the amino acid.
  • most hydrophobic amino acids are isoleucine (4.5) and valine (4.2), hydrophobic amino acids tend to be internal
  • most hydrophilic amino acids are arginine (-4.5) and lysine (-3.9), hydrophilic amino acids are more commonly found towards the protein surface.


Links: Protein

Signaling Factors

Hedgehog signaling pathway.jpg

Hedgehog signaling pathway[5]

Note spelling difference: USA signaling, UK signalling.

Factor Links: AMH | hCG | BMP | sonic hedgehog | bHLH | HOX | FGF | FOX | Hippo | LIM | Nanog | NGF | Nodal | Notch | PAX | retinoic acid | SIX | Slit2/Robo1 | SOX | TBX | TGF-beta | VEGF | WNT | Category:Molecular

Axis Formation

Embryo left-right asymmetry pathway.jpg

Embryo left-right asymmetry pathway[6]

The mechanisms that specify location within the embryo, therefore establishing axes, appears to be controlled by similar signaling mechanisms in different species.


Links: Axis Formation

Epigenetics

Epigenetics as the name implies, is the inheritance mechanisms that lie outside the DNA sequence of our genes.

One of the initial discoveries was the effects of DNA methylation upon gene expression and then modifications of nucleosomal histones.

This DNA methylation, usually associated with 5-methylcytosine (m5C), leads to transcriptional silencing in vertebrates.

Links: Epigenetics
Epigenetics mechanisms

References

  1. <pubmed>16688142</pubmed>
  2. 2.0 2.1 <pubmed>108157</pubmed>
  3. <pubmed>19104053</pubmed>| PNAS
  4. 4.0 4.1 <pubmed>7108955</pubmed>
  5. <pubmed>19040769</pubmed>| PMC2614485 | Genome Biology
  6. <pubmed>23256866</pubmed>| BMC Biology


Terms

Includes some brief descriptions of additional factors and their receptors.

  • Netrin - roles in cell migration and neural axon guidance (secreted and GPI-anchored proteins). Secreted netrins can act either positively (attractive) or negatively (repulsive).
  • Neurotrophin - secreted proteins interact with membrane tyrosine kinase receptors.
  • Robo receptor - a member of the immunoglobulin superfamily.
  • Semaphorin - (Sem) 8 vertebrate classes (class 3 secreted, classes 4 - 6 are transmembrane proteins, class 7 are GPI-anchored proteins). Secreted semaphorins bind the neuropilins, while the transmembrane semaphorins interact with the plexus, and GPI-anchored semaphorins are thought to use integrins as their receptors.
  • Slit - Slit proteins signal through Roundabout (Robo) receptors and can mediate chemorepulsive events during development.


External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.


Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link



Cite this page: Hill, M.A. (2024, March 28) Embryology Molecular Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Molecular_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G