Positional cloning of heart and soul reveals multiple roles for PKCλ in zebrafish organogenesis

Abstract

Our results show that aPKC lambda is required for the formation and maintenance of the zonula adherens during early epithelial development in vertebrates and demonstrate a previously undescribed yet critical role for this protein in organ morphogenesis. Furthermore, our studies identify the first genetic locus regulating the orientation of cell division in vertebrates.

Cardiac patterning and morphogenesis in zebrafish

“…As a result, the atrium cannot form properly and the has mutant heart exhibits atrial tissue outside of the ventricle (Fishman and Chien, 1997;Yelon et al, 1999). Recently, the has locus has been shown to encode an atypical PKC molecule, similar to PKC (Horne-Badovinac et al, 2001;Peterson et al, 2001). In Drosophila, PKC forms a complex with two other proteins (Par-3/Bazooka and Par-6) (Muller and Wieschaus, 1996;Kuchinke et al, 1998;Wodarz et al, 2000;Petronczki and Knoblich, 2001).…”

“…This complex is found at the apicolateral membrane of epithelial cells, and integrity of the complex is required for the maintenance of epithelial polarity. In has mutants, defects in epithelial polarity have been described in the swim bladder, the retina, and the neural tube but the relationship of epithelial polarity to heart tube assembly is not yet clear (Horne-Badovinac et al, 2001). Perhaps the migrating and fusing myocardiocytes behave as a polarized epithelium.…”

Rôle des protéines Crumbs dans le contrôle de la morphogenèse des cellules épithéliales et des photorécepteurs

“…D'autres protéines du complexe crumbs ou du complexe Par3/Par6/PKCa ont également montré leur importance dans la formation de l'oeil chez le poisson zèbre (Danio rerio): c'est le cas de l'homologue de Pals1, étudié dans le mutant nagie oko [42], et de la PKCa l, dans le mutant heart and soul [43]. Il est donc possible que d'autres membres de ces deux complexes puissent, chez l'homme, être responsables de RP.…”

Modeling human hematopoietic and cardiovascular diseases in zebrafish

“…The heart and soul (has) mutant has a defect in cardiac fusion that influences polarity of the developing heart tube, as well as other organs Stainier et al, 1996). An atypical protein kinase C (aPKC ) that functions in epithelial polarity and tight junction integrity is encoded by the has locus (Horne-Badovinac et al, 2001;Peterson et al, 2001). The hearts of has mutant embryos fail to develop distinctive chambers, with ventricular muscle appearing inside of the atrium (Horne-Badovinac et al, 2001;Peterson et al, 2001).…”

“…An atypical protein kinase C (aPKC ) that functions in epithelial polarity and tight junction integrity is encoded by the has locus (Horne-Badovinac et al, 2001;Peterson et al, 2001). The hearts of has mutant embryos fail to develop distinctive chambers, with ventricular muscle appearing inside of the atrium (Horne-Badovinac et al, 2001;Peterson et al, 2001). In a recent screen for chemical agents that affect heart formation, the chemical concentramide was found to phenocopy the heart defect in has mutants, with the ventricle forming inside the atrium in treated embryos (Peterson et al, 2001).…”