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 Δ 5 /Δ 5 ) and embryos with an exon 7 deletion ( Alk2 Δ 7 /Δ 7 ). Both Alk2 Δ 5 /Δ 5 and Alk2 Δ 7 /Δ 7 mutants showed identical morphological gastrulation defects. Histological examinations and molecular marker analyses revealed identical abnormal gastrulation phenotypes in Alk2 Δ 5 /Δ 5 and Alk2 Δ 7 /Δ 7 mutants. Although Fgf8 was expressed in the primitive streak of Alk2 Δ 5 /Δ 5 and Alk2 Δ 7 /Δ 7 mutants, Brachyury , Wnt3a , and Tbx6 were dramatically downregulated in Alk2 Δ 5 /Δ 5 and Alk2 Δ 7 /Δ 7 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. Developmental Dynamics 236:512–517, 2007. Published 2006 Wiley‐Liss, Inc.