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Published on: January 20, 2019
Pax3 functions in cell survival and in pax7 regulation
A G Borycki1, J Li, F Jin
1Department of Cell and Developmental Biology, Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. epsteinj@mail.med.upenn.edu
Insights
Pax3 is crucial for muscle development and cell survival in vertebrate embryos. It activates MyoD, prevents cell death, and represses Pax7, ensuring proper neural tube and somite formation.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Pax3 is a key transcription factor in vertebrate embryonic development.
- It is expressed in the neural tube and paraxial mesoderm, essential for skeletal muscle formation.
- Pax3 mutations lead to muscular and neural tube defects, highlighting its critical role in myogenesis.
Purpose of the Study:
- To investigate the specific functions of Pax3 in cell survival and gene expression during embryonic development.
- To elucidate the role of Pax3 in MyoD activation and apoptosis within the presomitic mesoderm, somites, and neural tube.
- To understand the regulatory relationship between Pax3 and Pax7 in neural tube and somite development.
Main Methods:
- Analysis of wild-type and Pax3 mutant (Splotch) mouse embryos.
- Examination of cell survival and gene expression in presomitic mesoderm, somites, and neural tube.
- Disruption of Pax3 expression using antisense oligonucleotides in cultured presomitic mesoderm.
Main Results:
- Pax3 disruption impairs MyoD activation and increases programmed cell death (apoptosis) in cultured presomitic mesoderm.
- In Pax3 mutant embryos, MyoD-expressing cells are disorganized, and apoptosis is prevalent in newly formed somites.
- Pax7 is upregulated and expanded into regions of Pax3 expression in neural tube and somites where cell survival is maintained.
Conclusions:
- Pax3 plays complementary roles in activating MyoD and inhibiting apoptosis in somitic mesoderm.
- Pax3 is essential for repressing Pax7 expression in the neural tube and somites.
- These findings establish Pax3's critical functions in regulating cell survival, gene activation, and spatial gene expression during vertebrate embryonic development.
Abstract:
In developing vertebrate embryos, Pax3 is expressed in the neural tube and in the paraxial mesoderm that gives rise to skeletal muscles. Pax3 mutants develop muscular and neural tube defects; furthermore, Pax3 is essential for the proper activation of the myogenic determination factor gene, MyoD, during early muscle development and PAX3 chromosomal translocations result in muscle tumors, providing evidence that Pax3 has diverse functions in myogenesis. To investigate the specific functions of Pax3 in development, we have examined cell survival and gene expression in presomitic mesoderm, somites and neural tube of developing wild-type and Pax3 mutant (Splotch) mouse embryos. Disruption of Pax3 expression by antisense oligonucleotides significantly impairs MyoD activation by signals from neural tube/notochord and surface ectoderm in cultured presomitic mesoderm (PSM), and is accompanied by a marked increase in programmed cell death. In Pax3 mutant (Splotch) embryos, MyoD is activated normally in the hypaxial somite, but MyoD-expressing cells are disorganized and apoptosis is prevalent in newly formed somites, but not in the neural tube or mature somites. In neural tube and somite regions where cell survival is maintained, the closely related Pax7 gene is upregulated, and its expression becomes expanded into the dorsal neural tube and somites, where Pax3 would normally be expressed. These results establish that Pax3 has complementary functions in MyoD activation and inhibition of apoptosis in the somitic mesoderm and in repression of Pax7 during neural tube and somite development.
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