BMP type I receptor ALK2 is essential for proper patterning at late gastrulation during mouse embryogenesis.
Bone morphogenetic proteins (BMPs) have multiple functions during vertebrate development. Previously, it was shown that BMP type I receptor ALK2 (also known as ACVRI, ActRI, or ActRIA) was important for normal mouse gastrulation by deleting exon 4 or exon 5 of Alk2. Recently, flanking exon 7 by loxP sites generated a conditional allele for Alk2. To assess whether the deletion of exon 7 causes functional null of ALK2, and does not produce a dominant negative form or a partially functional form of ALK2, we performed a comparative analysis between Alk2 homozygous mutant embryos with an exon 5 deletion (Alk2(Delta5/Delta5)) and embryos with an exon 7 deletion (Alk2(Delta7/Delta7)). Both Alk2(Delta5/Delta5) and Alk2(Delta7/Delta7) mutants showed identical morphological gastrulation defects. Histological examinations and molecular marker analyses revealed identical abnormal gastrulation phenotypes in Alk2(Delta5/Delta5) and Alk2(Delta7/Delta7) mutants. Although Fgf8 was expressed in the primitive streak of Alk2(Delta5/Delta5) and Alk2(Delta7/Delta7) mutants, Brachyury, Wnt3a, and Tbx6 were dramatically downregulated in Alk2(Delta5/Delta5) and Alk2(Delta7/Delta7) mutants. These results indicate that deletion of exon 7 for Alk2 leads to a functionally null mutation in vivo, and Alk2 is crucial for sustaining the proper gastrulation events in early mouse embryogenesis.
Komatsu
Yoshihiro
Y
Molecular Developmental Biology Group, Laboratory of Reproductive and Developmental Toxicology, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Scott
Gregory
G
Nagy
Andre
A
Kaartinen
Vesa
V
Mishina
Yuji
Y
D030201:Activin Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005091:Exons / Q000235:genetics*; D005775:Gastrula / Q000502:physiology*; D005838:Genotype; D017403:In Situ Hybridization; D051379:Mice; D010641:Phenotype; D017384:Sequence Deletion / Q000235:genetics*
D030201:Activin Receptors, Type I; C498943:Acvr1 protein, mouse