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1.
Proc Natl Acad Sci U S A ; 121(35): e2405217121, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39172791

RESUMO

Intercellular signaling mediated by evolutionarily conserved planar cell polarity (PCP) proteins aligns cell polarity along the tissue plane and drives polarized cell behaviors during tissue morphogenesis. Accumulating evidence indicates that the vertebrate PCP pathway is regulated by noncanonical, ß-catenin-independent Wnt signaling; however, the signaling components and mechanisms are incompletely understood. In the mouse hearing organ, both PCP and noncanonical Wnt (ncWnt) signaling are required in the developing auditory sensory epithelium to control cochlear duct elongation and planar polarity of resident sensory hair cells (HCs), including the shape and orientation of the stereociliary hair bundle essential for sound detection. We have recently discovered a Wnt/G-protein/PI3K pathway that coordinates HC planar polarity and intercellular PCP signaling. Here, we identify Wnt7b as a ncWnt ligand acting in concert with Wnt5a to promote tissue elongation in diverse developmental processes. In the cochlea, Wnt5a and Wnt7b are redundantly required for cochlear duct coiling and elongation, HC planar polarity, and asymmetric localization of core PCP proteins Fzd6 and Dvl2. Mechanistically, Wnt5a/Wnt7b-mediated ncWnt signaling promotes membrane recruitment of Daple, a nonreceptor guanine nucleotide exchange factor for Gαi, and activates PI3K/AKT and ERK signaling, which promote asymmetric Fzd6 localization. Thus, ncWnt and PCP signaling pathways have distinct mutant phenotypes and signaling components, suggesting that they act as separate, parallel pathways with nonoverlapping functions in cochlear morphogenesis. NcWnt signaling drives tissue elongation and reinforces intercellular PCP signaling by regulating the trafficking of PCP-specific Frizzled receptors.


Assuntos
Polaridade Celular , Proteínas Wnt , Via de Sinalização Wnt , Proteína Wnt-5a , Animais , Polaridade Celular/fisiologia , Proteínas Wnt/metabolismo , Proteínas Wnt/genética , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/genética , Camundongos , Via de Sinalização Wnt/fisiologia , Cóclea/metabolismo , Cóclea/citologia , Cóclea/crescimento & desenvolvimento , Células Ciliadas Auditivas/metabolismo , Receptores Frizzled/metabolismo , Receptores Frizzled/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Morfogênese
2.
Genesis ; 55(6)2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28319357

RESUMO

The lens originates from a simple cuboidal epithelium, which, on its basal side, contacts the optic vesicle, whilst facing the extraembryonic environment on its apical side. As this epithelium changes into the pseudostratified lens placode, its cells elongate and become narrower at their apical ends. This is due to the formation of an apical actin network, whose appearance is restricted to cells of the placodal region, as a result of region-specific signaling mechanisms that remain largely unknown. Here, we investigated the role of the polarity protein PAR3 and the phosphorylation state of its Threonine 833 (T833) aPKC-binding site in the recruitment of aPKC and in the establishment of actin network in the chick lens placode. Overexpression of wild type PAR3 recruited aPKC and punctate actin clusters to the basolateral membranes of the placodal cells. Recruitment of aPKC depended on the charge of the residue that replaced the T833 residue. In contrast, induction of the ectopic actin spots was independent on the charge of this residue.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Ectoderma/metabolismo , Cristalino/metabolismo , Actinas/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Polaridade Celular , Embrião de Galinha , Ectoderma/embriologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Cristalino/embriologia , Ligação Proteica , Proteína Quinase C/metabolismo
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