Essential role for the SLK protein kinase in embryogenesis and placental tissue development

Background: Over the past decade, the Ste20‐like kinase SLK, has been implicated in several signaling processes. SLK repression has been shown to impair cell cycle kinetics and inhibit FAK‐mediated cell migration. Here, using a gene trapped allele, we have generated mice expressing a truncated form...

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Published in:Developmental dynamics 2014-05, Vol.243 (5), p.640-651
Main Authors: Al‐Zahrani, Khalid N., Sekhon, Prabhjot, Tessier, Daniel R., Yockell‐Lelievre, Julien, Pryce, Benjamin R., Baron, Kyla D., Howe, Grant A., Sriram, Roshan K., Daniel, Kate, Mckay, Marlene, Lo, Vivian, Quizi, Jennifer, Addison, Christina L., Gruslin, Andrée, Sabourin, Luc A.
Format: Article
Language:English
Subjects:
Animals
Embryo, Mammalian - cytology
Embryo, Mammalian - enzymology
Embryogenesis
Embryonic Development - physiology
Female
Gene trap
Mice
Mice, Transgenic
Placenta
Placenta - cytology
Placenta - enzymology
Pregnancy
Pregnancy Proteins - genetics
Pregnancy Proteins - metabolism
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Ste‐20 like kinase
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Summary:Background: Over the past decade, the Ste20‐like kinase SLK, has been implicated in several signaling processes. SLK repression has been shown to impair cell cycle kinetics and inhibit FAK‐mediated cell migration. Here, using a gene trapped allele, we have generated mice expressing a truncated form of the SLK kinase. Results: Our results show that an SLK‐LacZ fusion protein is expressed in embryonic stem cells and in embryos throughout development. We find that the SLK‐LacZ fusion protein is less efficient at phosphorylating substrates resulting in reduced cell proliferation within the embryos and angiogenic defects in the placentae of the homozygous mutant animals at embryonic day (E) 12.5. This results in marked developmental defects and apoptotic lesions in the embryos by E14.5. Conclusions: Homozygotes expressing the SLK‐LacZ fusion protein present with an embryonic lethal phenotype occurring between E12.5 and E14.5. Overall, we demonstrate a requirement for SLK kinase activity in the developing embryo and placenta. Developmental Dynamics 243:640–651, 2014. © 2013 Wiley Periodicals, Inc. Key Findings SLK is expressed throughout the developing mouse embryo. Absence of SLK results embryonic defects predominantly in the myogenic and neurogenic compartments. SLK deletion results in impaired vascularization and placental defects.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.24106