This page is a link to many different resources related to Molecular Development. In current years we have turned from wanting to merely describe the events of embryogenesis, to a desire to understand the mechanisms of development.
Fly Heads of wildtype and antennapedia (Hox) mutant (Images Dr. Rudi Turner)
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.
Page Links: Introduction | Some Recent Findings | Starting Out | Mechanisms and Factors | System Notes Molecular | Glossary
Cartilage Development Kobayashi T, Lu J, Cobb BS, Rodda SJ, McMahon AP, Schipani E, Merkenschlager M, Kronenberg HM. Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci U S A. 2008 Jan 31;
"Small noncoding RNAs, microRNAs (miRNAs), bind to messenger RNAs through base pairing to suppress gene expression. ... Dicer, an essential component for biogenesis of miRNAs ...critical role of the Dicer-dependent pathway in the regulation of chondrocyte proliferation and differentiation during skeletal development."
(More? Cartilage Development | Musculoskeletal Development )
Muscle Development Du SJ, Li H, Bian Y, Zhong Y. Heat-shock protein 90alpha1 is required for organized myofibril assembly in skeletal muscles of zebrafish embryos. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):554-9
"Heat-shock protein 90alpha (Hsp90alpha) is a member of the molecular chaperone family involved in protein folding and assembly specifically expressed in developing somites and skeletal muscles of zebrafish embryos ... and is essential for myofibril organization in skeletal muscles of zebrafish embryos. ...likely through facilitating myosin folding and assembly into organized myofibril filaments."
(More? Muscle Development | Zebrafish Development)
Endocrine Development Wang Q, Elghazi L, Martin S, Martins I, Srinivasan RS, Geng X, Sleeman M, Collombat P, Houghton J, Sosa-Pineda B. ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum. Dev Dyn. 2008 Jan;237(1):51-61.
"Pax4-deficient mice have a severe gastrointestinal endocrine deficiency: they lack most pancreatic cells that produce insulin or somatostatin and various duodenal endocrine cell types."
(More? Endocrine Development - Pancreas | Gastrointestinal Tract Development)
There are several different ways to begin to look at molecular development.
The first page of Developmental and System Notes usually contains some information about mechanisms of development that include molecular mechanisms. In order to keep the introductory page simple, detailed molecular mechanisms have been placed on a separate page (Page 11) of each section of notes. Below is a list of direct links to specific Molecular Development Pages.
| Molecular System Notes |
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| Axis Formation | Early | Limbs |
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| DNA Notes | |
| NCBI- Genes & Diseases |
Signaling during development, though complex, can also be grouped into a few specific classes. These mechanisms have also been introduced and described briefly on Signaling Mechanisms and Cell Cycle pages. (More? NCBI- Genes & Diseases)
Factor Pages: Bone Morphogenic Protein (BMP) | Engrailed (En) | Fibroblast Growth Factor (FGF) | Hedgehog (HH) | Homeobox genes (Hox) | Laminin | MyoD | Nanog | Nodal | Notch | Paired Box (Pax) | PItuitary-specific Transcription factor (Pit) | Retinoic Acid (RA) | Snail | | Sonic Hedgehog (SHH) | SRY | T-Box genes | Transforming Growth Factor-beta (TGF- beta) | Olig | Vascular Endothelial Growth Factor (VEGF) | Wnt7a
| Please note that these notes only relate to an earlier Course and not all Lecture notes and research material have been transferred. |
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Simple pictures illustrating the early events of fertilization. |
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Figures and text relating to early events of spinal cord formation. |
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Text relating to the molecular events of sex determination in the embryo. |
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A short comparison of establishing positional information in embryos. |
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The fly mutation that opened the field of Hox Genes and the conservation of pattern formation control mechanisms between species in embryonic development. |
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
antisense- a sequence of DNA that is complementary usually to coding sequence of DNA or mRNA. Has been used experimentally to perturb or block gene expression. Also a mechanism that has been found to occur naturally as a regulatory mechanism.
autosomal inheritance- some hereditary diseases are described as autosomal which means that the disease is due to a DNA error in one of the 22 pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked.
base- another term for nucleotide (usually a t c g).
base pair- Double stranded DNA has nucleotides A-T, C-G, paired by hydrogen bonds (2 for AT, 3 for GC). Note this means that GC is harder to separate that AT.
DNA- DeoxyriboNucleic Acid. The genetic material found in mammalian chromosomes and mitochondria. Consisting of 4 nucleic acids (ATCG) that combine in a triptych (3 nucleotide) code for protein amino acids (3nt=1aa).
DNA duplex- double stranded base-paired DNA forming a helix.
dominant inheritance-With autosomal dominant inheritance, there is an error in one of the 22 chromosome pairs. But the damaged gene dominates over the normal gene received from the other parent. If one of the parents has a disease caused by an autosomal dominant gene, all the children will have a 50 per cent risk of inheriting the dominant gene and a 50 per cent chance of not inheriting it. The children who do not inherit the damaged dominant gene will not themselves suffer from the disease, nor will they be able to pass the gene on to future children. This type of inheritance is present for example in Huntington's disease.
exon- a block of protein encoding sequence of DNA in a gene. Many proteins are made of several exons "stitched" or spliced together by editing out non-coding (intron) sequences.
fasta- a format for listing DNA sequence, where the first line has descritive information followed on the next line by the sequence without numbering.
GC repeat- a string of GC sequence repeated several times. Also associated with GC expansion, a mutational process that may lead eventually to serious gene expression effects.
gene- a sequence of DNA that encodes an individual protein.
genetic code- the 3 nucleotide sequence that forms a codon for a single amino acid or stop. See the gene code.
genome- the complete genetic information in the form of DNA available to a specific species.
hairpin loop- a folding of RNA generated by base pairing making a "===()" structure, the end loop and or stem of this structure can then interact with proteins or other RNA.
intron- a block of DNA within a gene not encoding a protein. Edited, spliced, out during transcription into mRNA. Originally thought not to contain any information, but more and more this appears not to be the case. Some intron sequences have been shown to regulate gene expression during development (eg c elegans, Lin 14)
MicroRNA - (miRNA) a small noncoding ribonucleotide-based (RNA) regulators of gene expression. These recently discovered small RNA molecules (18-24 nucleotides) negatively regulate target mRNAs and appear to have a role in many developmental processes as well as in the adult. (See also "Dicer") There is also another class of small RNAs involved in gene expression present in cells, small interfering RNAs (siRNAs), generated from double-stranded RNA (dsRNA) precursors.
mRNA- messenger, transcribed from DNA in the nucleus and in mitochondria. Is translated by the ribosome in the cytoplasm (or mitochondrial matrix). Intermediate step in gene expression. (DNA-> mRNA-> protein).
mutation- any process which results in the alteration of the DNA sequence. Some conservative mutations may have no effect on the final amino acid encoded.
point mutation- a change in a single nucleotide.
recessive inheritance-With autosomal recessive inheritance, the diseased individual has inherited the same gene damage from both father and mother. The damage is found on both chromosomes in the pair. But as this is not ´dominant gene damageª, neither father nor mother show any sign of disease, they are healthy carriers of the gene. We are all carriers of about five recessive genes of this type, but as spouses are seldom carriers of exactly the same damaged gene(s), all will probably go well in the next generation.
ribosome- complex of rRNA and ribosomal proteins, bind mRNA and translate it into protein.
RNA- RiboNucleic Acid. The intermediate nucleic acid involved in gene expression. It comes in 3 forms: tRNA, mRNA, rRNA.
rRNA- ribosomal, translates mRNA into protein. rRNA provides the "scaffolding" on which many ribosomal proteins are assembled as 2 subunits that themselves assemble to form a ribosome. rRNA genes are localized to the nucleolus in the nucleus, a sometimes visible region of DNA usually constantly being transcribed.
telomere- regions at the end of chromosomes. Shortening of the telomeres is thought to be associated with cellular aging. The enzyme that maintains the telomere is called telomerase. Introducing this gene into a cell can extend the cells lifespan.
transcription factor- a protein which binds to DNA activating (usually) gene expression. There are many different ways and forms that this activation can take place, but most transcription factors fall into specific classes (eg zinc fingers, helix loop helix).
tRNA- transfer, binds single amino acids acts as a "donor' for protein synthesis.
This current page has additional windows that allow searching of OMIM Morbid Map and OMIM Gene Map and access to other External WWW Search pages (Medical dictionaries, glossaries, chemicals and drugs).
In the DNA Notes there is a window to search the Human Genome by keyword and also to search for a specific species classification.
In the DNA Notes there is also a page with 3 search windows for Nucleotide Sequence, Protein Sequence and Biomolecule 3D Structure from NCBI.
In the Chemical Notes there is a window to search a Material Safety Data Sheet database for a specific chemical and its associated hazard.
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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.
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 11" covering molecular Development in that system.
Please email Dr Mark Hill if you wish to make a comment about this current project.