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Developmental potential of mouse primordial germ cells
Y Kato1, W M Rideout, K Hilton
1Wellcome CRC Institute of Cancer and Developmental Biology and Physiological Laboratory, Tennis Court Road, University of Cambridge, Cambridge CB2 1QR, UK.
Development (Cambridge, England)
|April 2, 1999
Summary
Primordial germ cells erase genomic imprints, making parental genomes equivalent. Transplanting these imprint-free nuclei into oocytes resulted in abnormal embryonic development, indicating gametic imprints are essential for normal mammalian development.
Area of Science:
- Epigenetics
- Genomics
- Developmental Biology
Background:
- Primordial germ cells (PGCs) undergo unique genomic modifications, including demethylation and erasure of imprints on imprinted genes.
- These epigenetic reprogramming events in PGCs erase parental genome distinctions, creating an equivalent epigenetic state.
- Imprinted genes regulate monoallelic expression and gene dosage, crucial for normal development.
Purpose of the Study:
- To investigate the functional significance of imprint erasure in PGCs for mammalian embryonic development.
- To determine if imprint-free PGC nuclei can support normal development when reconstituted into oocytes.
- To assess the necessity of gametic imprints for proper embryonic and placental development.
Main Methods:
- Nuclear transplantation of PGC nuclei into enucleated oocytes.
- Developmental assessment of reconstituted oocytes to day 9.5 of gestation.
- Analysis of DNA methylation and gene expression of imprinted genes in experimental conceptuses.
- Tetraploid complementation assay to rescue the inner cell mass of developing embryos.
Main Results:
- Reconstituted oocytes developed into small embryos with abnormal placentas by day 9.5.
- Embryonic development was significantly impaired, even with rescue via tetraploid complementation.
- Analysis revealed a lack of essential gametic imprints and aberrant expression of imprinted genes.
Conclusions:
- Gametic imprints are indispensable for normal mammalian embryonic and placental development.
- Mature oocytes lack the capacity to initiate or erase epigenetic imprints, a process unique to the developing germ line.
- The erasure of genomic imprints in PGCs is a critical step that primes the germline for subsequent development.