Mechanobiology June 26th - June 2nd 2016

Mechanobiology: June 26th  - June 2nd 2016


The conserved septin family of filamentous small GTPases plays important roles in mitosis, cell migration, and cell morphogenesis by forming scaffolds and diffusion barriers. Recent studies in tissue culture cells indicate that a septin complex of septin 2, 7 and 9 is required for ciliogenesis and cilia function, but septin function in ciliogenesis in vertebrate organs in vivo is not understood. We show that sept7b is expressed in ciliated cells in different tissues in early zebrafish development. Knockdown of sept7b by morpholino antisense oligonucleotides caused misorientation of basal bodies and cilia, reduction of apical actin, and shortening of motile cilia in Kupffer's vesicle and pronephric tubules. This resulted in pericardial and yolk sac edema, body axis curvature, and hydrocephaly. Significantly, in sept7b morphants we detected strong left-right asymmetry defects in the heart and lateral plate mesoderm (situs inversus), reduced fluid flow in the kidney, the formation of kidney cysts, and loss of glomerular filtration barrier function. Thus, sept7b is essential in zebrafish development for pronephric function and ciliogenesis, and loss of sept7b expression results in defects that resemble human ciliopathies.