title: PAR-1 promotes primary neurogenesis and asymmetric cell divisions via control of spindle orientation.
abstract: In both invertebrate and vertebrate embryonic central nervous systems, deep cells differentiate while superficial (ventricular) epithelial cells remain in a proliferative, stem cell state. The conserved polarity protein PAR-1, which is basolaterally localised in epithelia, promotes and is required for differentiating deep layer cell types, including ciliated cells and neurons. It has recently been shown that atypical protein kinase C (aPKC), which is apically enriched, inhibits neurogenesis and acts as a nuclear determinant, raising the question of how PAR-1 antagonises aPKC activity to promote neurogenesis. Here we show that PAR-1 stimulates the generation of deep cell progeny from the superficial epithelium of the neural plate and that these deep cells have a corresponding (i.e. deep cell) neuronal phenotype. We further show that gain- and loss-of-function of PAR-1 increase and decrease, respectively, the proportion of epithelial mitotic spindles with a vertical orientation, thereby respectively increasing and decreasing the number of cleavages that generate deep daughter cells. PAR-1 is therefore a crucial regulator of the balance between symmetric (two superficial daughters) and asymmetric (one superficial and one deep daughter) cell divisions. Vertebrate PAR-1 thus antagonises the anti-neurogenic influence of apical aPKC by physically partitioning cells away from it in vivo.
authors.affiliation: King's College London, Department of Craniofacial Development, Floor 27, Guy's Tower, London SE1 9RT, UK.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Tabler
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Jeremy B A
authors.initials: JB
authors.lastname: Green
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D015509:Developmental Biology / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D054258:Neural Plate / Q000378:metabolism; D055495:Neurogenesis; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D008941:Spindle Apparatus; D013997:Time Factors; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins; C496647:MARK3 protein, Xenopus; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C