title: Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development.
abstract: The insulin receptor substrate of 53 kDa, IRSp53, is an adaptor protein that works with activated GTPases, Cdc42 and Rac, to modulate actin dynamics and generate membrane protrusions in response to cell signaling. Adult mice that lack IRSp53 fail to regulate synaptic plasticity and exhibit hippocampus-associated learning deficiencies. Here, we show that 60% of IRSp53 null embryos die at mid to late gestation, indicating a vital IRSp53 function in embryonic development. We find that IRSp53 KO embryos displayed pleiotropic phenotypes such as developmental delay, oligodactyly and subcutaneous edema, and died of severely impaired cardiac and placental development. We further show that double knockout of IRSp53 and its closest family member, IRTKS, resulted in exacerbated placental abnormalities, particularly in spongiotrophoblast differentiation and development, giving rise to complete embryonic lethality. Hence, our findings demonstrate a hitherto under-appreciated IRSp53 function in embryonic development, and further establish an essential genetic interaction between IRSp53 and IRTKS in placental formation.
authors.affiliation: Neural Stem Cells Laboratory, Institute of Medical Biology, 138648 Singapore.
authors.forename: Ai Mei
authors.initials: AM
authors.lastname: Chou
authors.affiliation: Neural Stem Cells Laboratory, Institute of Medical Biology, 138648 Singapore.
authors.forename: Kai Ping
authors.initials: KP
authors.lastname: Sem
authors.affiliation: Epithelial Epigenetics and Development Laboratory, Institute of Medical Biology, 138648 Singapore.
authors.forename: Wei Jun
authors.initials: WJ
authors.lastname: Lam
authors.affiliation: Neural Stem Cells Laboratory, Institute of Medical Biology, 138648 Singapore.
authors.forename: Sohail
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Epithelial Epigenetics and Development Laboratory, Institute of Medical Biology, 138648 Singapore.
authors.forename: Chin Yan
authors.initials: CY
authors.lastname: Lim
mesh_terms: D000818:Animals; D020964:Embryo Loss / Q000235:genetics / Q000473:pathology; D047108:Embryonic Development; D005260:Female; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D058685:Genetic Pleiotropy; D006321:Heart / Q000196:embryology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010641:Phenotype; D010920:Placenta / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy
chemical_list: C539986:Baiap2 protein, mouse; C000606831:IRTKS protein, mouse; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins