Focal adhesion kinase is essential for cardiac looping and multichamber heart formation.
Focal adhesion kinase (FAK) is a critical mediator of matrix- and growth factor-induced signaling during development. Myocyte-restricted FAK deletion in mid-gestation mice results in impaired ventricular septation and cardiac compaction. However, whether FAK regulates early cardiogenic steps remains unknown. To explore a role for FAK in multi-chambered heart formation, we utilized anti-sense morpholinos to deplete FAK in Xenopus laevis. Xenopus FAK morphants exhibited impaired cardiogenesis, pronounced pericardial edema, and lethality by tadpole stages. Spatial-temporal assessment of cardiac marker gene expression revealed that FAK was not necessary for midline migration, differentiation, fusion of cardiac precursors, or linear heart tube formation. However, myocyte proliferation was significantly reduced in FAK morphant heart tubes and these tubes failed to undergo proper looping morphogenesis. Collectively our data imply that FAK plays an essential role in chamber outgrowth and looping morphogenesis likely stimulated by fibroblast growth factors (and possibly other) cardiotrophic factors.
Doherty
Jason T
JT
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Conlon
Frank L
FL
Mack
Christopher P
CP
Taylor
Joan M
JM
D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006321:Heart / Q000187:drug effects / Q000196:embryology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008845:Microinjections; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000235:genetics; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014335:Tropomyosin / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
D016376:Oligonucleotides, Antisense; D011758:Pyrroles; C105686:SU 5402; D014335:Tropomyosin; D016222:Fibroblast Growth Factor 2; D051416:Focal Adhesion Protein-Tyrosine Kinases; D053148:Caspase 3