Comparative analysis of zebrafish bone morphogenetic proteins 2, 4 and 16: molecular and evolutionary perspectives.
BMP2, BMP4 and BMP16 form a subfamily of bone morphogenetic proteins acting as pleiotropic growth factors during development and as bone inducers during osteogenesis. BMP16 is the most recent member of this subfamily and basic data regarding protein structure and function, and spatio-temporal gene expression is still scarce. In this work, insights on BMP16 were provided through the comparative analysis of structural and functional data for zebrafish BMP2a, BMP2b, BMP4 and BMP16 genes and proteins, determined from three-dimensional models, patterns of gene expression during development and in adult tissues, regulation by retinoic acid and capacity to activate BMP-signaling pathway. Structures of Bmp2a, Bmp2b, Bmp4 and Bmp16 were found to be remarkably similar; with residues involved in receptor binding being highly conserved. All proteins could activate the BMP-signaling pathway, suggesting that they share a common function. On the contrary, stage- and tissue-specific expression of bmp2, bmp4 and bmp16 suggested the genes might be differentially regulated (e.g. different transcription factors, enhancers and/or regulatory modules) but also that they are involved in distinct physiological processes, although with the same function. Retinoic acid, a morphogen known to interact with BMP-signaling during bone formation, was shown to down-regulate the expression of bmp2, bmp4 and bmp16, although to different extents. Taxonomic and phylogenetic analyses indicated that bmp16 diverged before bmp2 and bmp4, is not restricted to teleost fish lineage as previously reported, and that it probably arose from a whole genomic duplication event that occurred early in vertebrate evolution and disappeared in various tetrapod lineages through independent events.
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.|PhD Program in Biomedical Sciences, University of Algarve, Faro, Portugal.|Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Faro, Portugal.
Cátia L
CL
Marques
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
Ignacio
I
Fernández
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
Michael N
MN
Viegas
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
Cymon J
CJ
Cox
Centre for Molecular and Structural Biomedicine (CBME/IBB-LA), University of Algarve, Faro, Portugal.
Paulo
P
Martel
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.|PhD Program in Biomedical Sciences, University of Algarve, Faro, Portugal.|Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Faro, Portugal.
Joana
J
Rosa
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.|Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Faro, Portugal.
M Leonor
ML
Cancela
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal. vlaize@ualg.pt.|Department of Biomedical Sciences and Medicine (DCBM), University of Algarve, Faro, Portugal. vlaize@ualg.pt.
Vincent
V
Laizé
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055418:Bone Morphogenetic Protein 6 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D014212:Tretinoin / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
C000608270:BMP16 protein, zebrafish; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D029961:Zebrafish Proteins; C405936:bmp2b protein, zebrafish; C525813:bmp4 protein, zebrafish; D014212:Tretinoin
BMP-signaling; BMP2/4/16 subfamily; Bone morphogenetic proteins; Evolution; Gene expression; Retinoic acid; Zebrafish Danio rerio