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 ACVR1, ActR1, or ActRIA) was important for normal mouse gastrulation by deleting exon 4 or exon 5 of AM. 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 (Delta 5/Delta 5)) and embryos with an exon 7 deletion (Alk2 (Delta 7/Delta 7)). Both Alk2(Delta 5/Delta 5) and Alk2(Delta 7/Delta 7) mutants showed identical morphological gastrulation defects. Histological examinations and molecular marker analyses revealed identical abnormal gastrulation phenotypes in Alk2(Delta 5/Delta 5) and Alk2(Delta 7/Delta 7) mutants. Although FgfS was expressed in the primitive streak of Alk2(Delta 5/Delta 5) and Alk2 (Delta 7/Delta 7) mutants, Brachyury, Wnt3a, and Tbx6 were dramatically downregulated in Alk2 (Delta 5/Delta 5) and Alk2(Delta 7/Delta 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.