A parental requirement for dual-specificity phosphatase 6 in zebrafish
| Autor: | Charles G. Sagerström, Jennifer M. Maurer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male Embryo Nonmammalian Cell division MAP kinase phosphatase Morpholinos 0302 clinical medicine Testis Germ cell development Zebrafish lcsh:QH301-705.5 Gene Editing biology Homozygote Gene Expression Regulation Developmental Embryo Cell biology ERK signaling medicine.anatomical_structure Phenotype CRISPR Gene Knockdown Techniques Female Germ cell Cell Division Research Article DUSP6 Embryonic Development 03 medical and health sciences Dual Specificity Phosphatase 6 medicine Animals Zebrafish embryonic patterning Mitosis Alleles Base Sequence Gastrulation Ovary Zebrafish Proteins biology.organism_classification Rhombencephalon 030104 developmental biology Germ Cells lcsh:Biology (General) Mutation biology.protein Dual-specific phosphatase CRISPR-Cas Systems Developmental biology 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | BMC Developmental Biology BMC Developmental Biology, Vol 18, Iss 1, Pp 1-16 (2018) |
| ISSN: | 1471-213X |
| Popis: | Background Signaling cascades, such as the extracellular signal-regulated kinase (ERK) pathway, play vital roles in early vertebrate development. Signals through these pathways are initiated by a growth factor or hormone, are transduced through a kinase cascade, and result in the expression of specific downstream genes that promote cellular proliferation, growth, or differentiation. Tight regulation of these signals is provided by positive or negative modulators at varying levels in the pathway, and is required for proper development and function. Two members of the dual-specificity phosphatase (Dusp) family, dusp6 and dusp2, are believed to be negative regulators of the ERK pathway and are expressed in both embryonic and adult zebrafish, but their specific roles in embryogenesis remain to be fully understood. Results Using CRISPR/Cas9 genome editing technology, we generated zebrafish lines harboring germ line deletions in dusp6 and dusp2. We do not detect any overt defects in dusp2 mutants, but we find that approximately 50% of offspring from homozygous dusp6 mutants do not proceed through embryonic development. These embryos are fertilized, but are unable to proceed past the first zygotic mitosis and stall at the 1-cell stage for several hours before dying by 10 h post fertilization. We demonstrate that dusp6 is expressed in gonads of both male and female zebrafish, suggesting that loss of dusp6 causes defects in germ cell production. Notably, the 50% of homozygous dusp6 mutants that complete the first cell division appear to progress through embryogenesis normally and give rise to fertile adults. Conclusions The fact that offspring of homozygous dusp6 mutants stall prior to activation of the zygotic genome, suggests that loss of dusp6 affects gametogenesis and/or parentally-directed early development. Further, since only approximately 50% of homozygous dusp6 mutants are affected, we postulate that ERK signaling is tightly regulated and that dusp6 is required to keep ERK signaling within a range that is permissive for proper embryogenesis. Lastly, since dusp6 is expressed throughout zebrafish embryogenesis, but dusp6 mutants do not exhibit defects after the first cell division, it is possible that other regulators of the ERK pathway compensate for loss of dusp6 at later stages. Electronic supplementary material The online version of this article (10.1186/s12861-018-0164-6) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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