title: Requirement for integrin-linked kinase in neural crest migration and differentiation and outflow tract morphogenesis.
abstract: BACKGROUND
  Neural crest defects lead to congenital heart disease involving outflow tract malformation. Integrin-linked-kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in the neural crest, but its role in neural crest and outflow tract morphogenesis remains unknown.
  
  
  RESULTS
  We ablated ILK specifically in the neural crest using the Wnt1-Cre transgene. ILK ablation resulted in abnormal migration and overpopulation of neural crest cells in the pharyngeal arches and outflow tract and a significant reduction in the expression of neural cell adhesion molecule (NCAM) and extracellular matrix components. ILK mutant embryos exhibited an enlarged common arterial trunk and ventricular septal defect. Reduced smooth muscle differentiation, but increased ossification and neurogenesis/innervation were observed in ILK mutant outflow tract that may partly be due to reduced transforming growth factor β2 (TGFβ2) but increased bone morphogenetic protein (BMP) signaling. Consistent with these observations, microarray analysis of fluorescence-activated cell sorting (FACS)-sorted neural crest cells revealed reduced expression of genes associated with muscle differentiation, but increased expression of genes of neurogenesis and osteogenesis.
  
  
  CONCLUSIONS
  Our results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell matrix and multiple signaling pathways. Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Dai
authors.forename: Weijian
authors.initials: W
authors.lastname: Jiang
authors.forename: Qingquan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lian
authors.initials: L
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Geng
authors.forename: Shaowei
authors.initials: S
authors.lastname: Zhuang
authors.forename: Brian G
authors.initials: BG
authors.lastname: Petrich
authors.forename: Cizhong
authors.initials: C
authors.lastname: Jiang
authors.forename: Luying
authors.initials: L
authors.lastname: Peng
authors.forename: Shoumo
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.affiliation: Key Laboratory of Arrhythmia, Ministry of Education, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China. yfsunjie@gmail.com.
authors.forename: Yunfu
authors.initials: Y
authors.lastname: Sun
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Xingqun
authors.initials: X
authors.lastname: Liang
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D004622:Embryo, Mammalian; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics; D000099200:Scaffold Protein ILK
chemical_list: D019485:Bone Morphogenetic Proteins; D019006:Neural Cell Adhesion Molecules; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D053781:Transforming Growth Factor beta2; D051155:Wnt1 Protein; D000099200:Scaffold Protein ILK; C509042:Tgfb2 protein, mouse; C495246:Wnt1 protein, mouse