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Multiple roles for activin-like kinase-2 signaling during mouse embryogenesis
Y Mishina1, R Crombie, A Bradley
1Department of Molecular Genetics, University of Texas, M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
Developmental Biology
|September 10, 1999
Summary
Signaling through the Alk2 receptor is crucial for early embryonic development in mice, particularly for mesoderm formation during gastrulation and subsequent development. Loss of Alk2 function leads to severe developmental arrest.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Transforming growth factor-beta (TGF-beta) superfamily members regulate vertebrate embryogenesis.
- Alk2 (also known as ActRIA) is a type I receptor for activins and BMP-7.
- Alk2 transcripts are initially found in the visceral endoderm of mouse embryos.
Purpose of the Study:
- To investigate the role of Alk2 during mammalian development.
- To determine the necessity of Alk2 signaling in extraembryonic tissues for gastrulation and mesoderm formation.
Main Methods:
- Generation of Alk2 mutant mice.
- Construction of chimeric embryos using Alk2 mutant and wild-type embryonic stem (ES) cells.
- Morphological and molecular examination of embryos at various developmental stages.
Main Results:
- Alk2 homozygous mutant embryos exhibited developmental arrest around the late streak stage with gastrulation defects.
- Chimeric embryos showed rescue of gastrulation defects when Alk2 mutant ES cells contributed to wild-type blastocysts.
- Alk2 signaling is essential in extraembryonic tissues for mesoderm formation and post-gastrulation development.
Conclusions:
- Alk2 signaling is indispensable for normal mesoderm formation during gastrulation.
- Subsequent Alk2 signaling is required for proper development beyond gastrulation.
- The study highlights the critical role of Alk2 in extraembryonic tissues for embryonic viability.