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Published on: July 21, 2021
Genetic interaction between Bmp2 and Bmp4 reveals shared functions during multiple aspects of mouse organogenesis
Devorah C Goldman1, Nathan Donley, Jan L Christian
1Department of Cell and Developmental Biology, Oregon Health and Sciences University, School of Medicine, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Abstract:
Vertebrate Bmp2 and Bmp4 diverged from a common ancestral gene and encode closely related proteins. Mice homozygous for null mutations in either gene show early embryonic lethality, thereby precluding analysis of shared functions. In the current studies, we present phenotypic analysis of compound mutant mice heterozygous for a null allele of Bmp2 in combination with null or hypomorphic alleles of Bmp4. Whereas mice lacking a single copy of Bmp2 or Bmp4 are viable and have subtle developmental defects, compound mutants show embryonic and postnatal lethality due to defects in multiple organ systems including the allantois, placental vasculature, ventral body wall, skeleton, eye and heart. Within the heart, BMP2 and BMP4 function coordinately to direct normal lengthening of the outflow tract, proper positioning of the outflow vessels, and septation of the atria, ventricle and atrioventricular canal. Our results identify numerous BMP4-dependent developmental processes that are also very sensitive to BMP2 dosage, thus revealing novel functions of Bmp2.
Insights
Bone morphogenetic proteins (BMPs) BMP2 and BMP4 are crucial for embryonic development. Compound mutant mice revealed essential roles for BMP2 and BMP4 in multiple organ systems, highlighting novel BMP2 functions.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Biochemistry
Background:
- Vertebrate Bone Morphogenetic Proteins (BMPs) BMP2 and BMP4 are closely related paralogs originating from a common ancestral gene.
- Homozygous loss-of-function mutations in either Bmp2 or Bmp4 result in early embryonic lethality in mice, preventing detailed analysis of their shared functions.
Purpose of the Study:
- To investigate the shared and distinct functions of BMP2 and BMP4 during mouse embryonic development.
- To elucidate the phenotypic consequences of reduced BMP2 and BMP4 dosage in compound heterozygous mutant mice.
Main Methods:
- Generation and phenotypic analysis of compound mutant mice carrying a Bmp2 null allele and Bmp4 null or hypomorphic alleles.
- Detailed examination of developmental defects in multiple organ systems, including the heart, allantois, placental vasculature, ventral body wall, skeleton, and eye.
Main Results:
- Compound Bmp2/Bmp4 heterozygous mutants exhibit embryonic and postnatal lethality, indicating essential cooperative roles.
- Specific defects were observed in the allantois, placental vasculature, ventral body wall, skeleton, eye, and heart.
- Within the heart, BMP2 and BMP4 coordinate outflow tract lengthening, outflow vessel positioning, and septation of cardiac chambers and the atrioventricular canal.
Conclusions:
- BMP2 and BMP4 play critical, coordinated roles in the development of numerous organ systems.
- Many developmental processes dependent on BMP4 are also sensitive to BMP2 dosage, revealing novel functions for Bmp2.
- This study underscores the importance of BMP signaling in vertebrate embryonic patterning and organogenesis.
