Essential role for the Pak4 protein kinase in extraembryonic tissue development and vessel formation.
Pak4 is a member of the group B family of Pak serine/threonine kinases, originally identified as an effector protein for the Rho GTPase Cdc42. Pak4 knockout mice are embryonic lethal and do not survive past embryonic day 11.5. Previous work on Pak4 knockout mice has focused on studying the phenotype of the embryo. Abnormalities in the extraembryonic tissue, however, are common causes of early embryonic death in knockout mice. Extraembryonic tissue associated with the Pak4-null embryos was therefore examined. Abnormalities in both yolk sacs and placentas resulted when Pak4 was deleted. These included a lack of vasculature throughout the extraembryonic tissue, as well as an abnormally formed labyrinthine layer of the placenta. Interestingly, epiblast-specific deletion of Pak4 using a conditional knockout system, did not rescue the embryonic lethality. In fact, it did not even rescue the extraembryonic tissue defects. Our results suggest that the extraembryonic tissue abnormalities are secondary to defects that occur in response to epiblast abnormalities. More detailed analysis suggests that abnormalities in vasculature throughout the extraembryonic tissue and the epiblast may contribute to the death of the Pak4-null embryos.
Tian
Yanmei
Y
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Lei
Liang
L
Cammarano
Marta
M
Nekrasova
Tanya
T
Minden
Audrey
A
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009389:Neovascularization, Pathologic; D010641:Phenotype; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D013997:Time Factors; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism*
C492065:Pak4 protein, mouse; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein