Functional characterization and genetic mapping of alk8.
The novel type I TGFbeta family member receptor alk8 is expressed both maternally and zygotically. Functional characterization of alk8 was performed using microinjection studies of constitutively active (CA), kinase modified/dominant negative (DN), and truncated alk8 mRNAs. CA Alk8 expression produces ventralized embryos while DN Alk8 expression results in dorsalized phenotypes. Truncated alk8 expressing embryos display a subtle dorsalized phenotype closely resembling that of the identified zebrafish dorsalized mutant, lost-a-fin (laf). Single-strand conformation polymorphism (SSCP) analysis was used to map alk8 to zebrafish LG02 in a region demonstrating significant conserved synteny to Hsa2, and which contains the human alk2 gene, ACVRI. Altogether, these functional, gene mapping and phylogenetic analyses suggest that alk8 may be the zebrafish orthologue to human ACVRI (alk2), and therefore extend previous studies of Alk2 conducted in Xenopus.
Payne
T L
TL
Department of Cytokine Biology and Harvard-Forsyth Department of Oral Biology, The Forsyth Institute, Boston, MA 02115, USA.
Postlethwait
J H
JH
Yelick
P C
PC
D029404:Activin Receptors; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis; D002874:Chromosome Mapping; D017124:Conserved Sequence; D015536:Down-Regulation; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000378:metabolism; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D010802:Phylogeny; D018807:Polymorphism, Single-Stranded Conformational; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution; D014158:Transcription, Genetic; D015854:Up-Regulation; D029867:Xenopus Proteins; D015027:Zebrafish; D029961:Zebrafish Proteins
C525809:BMP4 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C405936:bmp2b protein, zebrafish; C525812:bmp4 protein, Xenopus; C525813:bmp4 protein, zebrafish; C054234:chordin; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors