title: Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth - SYDE1 regulates placental cell migration and invasion.
abstract: The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with pre-eclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (SYDE1), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion. Importantly, genetic ablation of murine Syde1 results in small fetuses and placentas with aberrant phenotypes in the placental-yolk sac barrier, maternal-trophoblast interface, and placental vascularization. Microarray analysis revealed altered expression of renin-1, angiotensin I converting enzyme 2, angiotensin II type 1a receptor, and membrane metalloendopeptidase of the renin-angiotensin system in Syde1-knockout placenta, which may compensate for the vascular defects to maintain normal blood pressure. As pregnancy proceeds, growth restriction of the Syde1-/-fetuses and placentas continues, with elevated expression of the Syde1 homologue Syde2 in placenta. Syde2 may compensate for the loss of Syde1 function because SYDE2, but not the GAP-dead SYDE2 mutant, reverses migration and invasion activities of SYDE1-knockdown JAR trophoblast cells. Clinically, we further detected decreased SYDE1 expression in preterm and term IUGR placentas compared with gestational age-matched controls. Our study suggests a novel mechanism for GCM1 and SYDE1 in regulation of trophoblast cell migration and invasion during placental development and that decreased SYDE1 expression is associated with IUGR. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Hsiao-Fan
authors.initials: HF
authors.lastname: Lo
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Ching-Yen
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Division of High Risk Pregnancy, Mackay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Chie-Pein
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Liang-Jie
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, Ming Chuan University, Tao-Yuan, Taiwan.
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Division of High Risk Pregnancy, Mackay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: National Laboratory Animal Center, Taipei, Taiwan.
authors.forename: Chung-Tiang
authors.initials: CT
authors.lastname: Liang
authors.affiliation: Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei 106, Taiwan.
authors.forename: Mei-Leng
authors.initials: ML
authors.lastname: Cheong
authors.affiliation: Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.|Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors.forename: Hungwen
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000235:genetics*; D011247:Pregnancy; D012084:Renin-Angiotensin System; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology
chemical_list: D004268:DNA-Binding Proteins; C491089:GCM1 protein, human; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C000618855:SYDE1 protein, human; C511357:Syndig1l protein, mouse; D014157:Transcription Factors
keywords: GCM1; IUGR, placenta; SYDE1; cell migration/invasion