Bone morphogenetic proteins (BMPs) are growth factors belonging to the transforming growth factor beta (TGFbeta) superfamily. These proteins have many different roles in development of different tissues and bind cell surface receptor kinases to activate intracellular (downstream) Smad proteins that translocate to the nucleus which can then act as transcription factors within cells.
BMPs do have an important role in bone morphogenesis, but their nomenclature is misleading as these factors have many other important roles in development of many different tissues.
The BMP precursor protein is 454 amino acids (Mr 51,736 Da).
Page Links: Introduction | Some Recent Findings | BMP Roles | BMP Inhibitors | Heart | Kidney | Testis | Database Entry Links | Signaling Factors | WWW Links | References | Glossary
Kidney - Bracken CM, Mizeracka K, McLaughlin KA. Patterning the embryonic kidney: BMP signaling mediates the differentiation of the pronephric tubules and duct in Xenopus laevis. Dev Dyn. 2008 Jan;237(1):132-44.
"BMP functions to mediate morphogenesis of the specified renal field during vertebrate embryogenesis. Specifically, BMP signaling is required for the differentiation of two types of nephric structures, the pronephric tubules and duct."
Itman C, Loveland KL. SMAD expression in the testis: an insight into BMP regulation of spermatogenesis. Dev Dyn. 2008 Jan;237(1):97-111.
"...Smad1, Smad5, Smad8, Smad4, Smad6, and Smad7 expression is ubiquitous during testis development but becomes cell-specific in the adult. Furthermore, regulated SMAD6 protein expression at the onset of spermatogenesis suggests differential responsiveness of spermatogonial subpopulations to ligands. In vitro, immature Sertoli cells and spermatogonia transduce BMP2 and BMP4 signals by means of SMAD1, SMAD5, and SMAD8."
patterning the dorsoventral axis
limb development
bone development - skeletal patterning, chondrogenesis and bone formation
Kidney development
Heart development
control of skin development and hair follicle growth
BMP antagonists (Sclerostin, chordin, CTGF, follistatin, and gremlin)
BMP inhibitors are the proteins that bind to BMP receptors but have no signaling function and therefore act as BMP receptor antagonists (inhibin and BMP-3).
Role in mesoderm formation
van Wijk B, Moorman AF, van den Hoff MJ. Role of bone morphogenetic proteins in cardiac differentiation. Cardiovasc Res. 2006 Nov 21
"This review summarizes the effects of BMP and the signaling pathways that regulate the differentiation of cardiomyocytes from mesoderm in the heart-forming region and at the distal borders of the heart tube from the second heart field. Subsequently, the role of BMPs in the formation of the ventricular chambers and septovalvulogenesis in the atrioventricular canal and outflow tract is described. Finally, the effects of BMPs in stem cell biology and cardiac regeneration are discussed."
Role in endocardial cushion formation
Gaussin et al., Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3PNAS 2002;99 2878-2883
"Receptors for bone morphogenetic proteins (BMPs), members of the transforming growth factor- (TGF) superfamily, are persistently expressed during cardiac development, yet mice lacking type II or type IA BMP receptors die at gastrulation and cannot be used to assess potential later roles in creation of the heart. Here, we used a Cre/lox system for cardiac myocyte-specific deletion of the type IA BMP receptor, ALK3. ALK3 was specifically required at mid-gestation for normal development of the trabeculae, compact myocardium, interventricular septum, and endocardial cushion. Cardiac muscle lacking ALK3 was specifically deficient in expressing TGF2, an established paracrine mediator of cushion morphogenesis. Hence, ALK3 is essential, beyond just the egg cylinder stage, for myocyte-dependent functions and signals in cardiac organogenesis."
Bracken CM, Mizeracka K, McLaughlin KA. Patterning the embryonic kidney: BMP signaling mediates the differentiation of the pronephric tubules and duct in Xenopus laevis. Dev Dyn. 2008 Jan;237(1):132-44.
"BMP functions to mediate morphogenesis of the specified renal field during vertebrate embryogenesis. Specifically, BMP signaling is required for the differentiation of two types of nephric structures, the pronephric tubules and duct."
Itman C, Loveland KL. SMAD expression in the testis: an insight into BMP regulation of spermatogenesis. Dev Dyn. 2008 Jan;237(1):97-111.
"...Smad1, Smad5, Smad8, Smad4, Smad6, and Smad7 expression is ubiquitous during testis development but becomes cell-specific in the adult. Furthermore, regulated SMAD6 protein expression at the onset of spermatogenesis suggests differential responsiveness of spermatogonial subpopulations to ligands. In vitro, immature Sertoli cells and spermatogonia transduce BMP2 and BMP4 signals by means of SMAD1, SMAD5, and SMAD8."
Many of the links below are to external resources and require an internet connection.
Links: Reviews | Articles | Search PubMed | Glossary
Reviews
Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors. 2004 Dec;22(4):233-41.
Search PubMed
Search Mar2008 "Bone morphogenetic protein" 8,582 reference articles of which 1,234 were reviews.
Search PubMed: term= Bone morphogenetic protein |
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 Introduction page.
Links: Journals | Online Textbooks | Search Textbooks | PubMed | Search PubMed | Glossary
Developmental Dynamics
Journal of Neurobiology
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002.
Developmental Biology (6th Edn) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.
Search NLM Online Textbooks- "hox" : Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach
Reviews
Articles
Search PubMed
Search Aug2005 "hox" ?? reference articles of which ?? were reviews.
Search PubMed: term= hox
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Note the dynamic developmental nature of the Internet means that some links may not always work (search using the link term).
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)
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.
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This section of notes introduces the topic of bone morphogenic proteins (BMP) which is a family of growth facotrs with many different functions.
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.
Please email Dr Mark Hill if you wish to make a comment about this current project.