title: Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis.
abstract: To gain insights into the cellular mechanisms of neurogenesis, we analyzed retinal neuroepithelia deficient for Llgl1, a protein implicated in apicobasal cell polarity, asymmetric cell division, cell shape and cell cycle exit. We found that vertebrate retinal neuroepithelia deficient for Llgl1 retained overt apicobasal polarity, but had expanded apical domains. Llgl1 retinal progenitors also had increased Notch activity and reduced rates of neurogenesis. Blocking Notch function by depleting Rbpj restored normal neurogenesis. Experimental expansion of the apical domain, through inhibition of Shroom3, also increased Notch activity and reduced neurogenesis. Significantly, in wild-type retina, neurogenic retinal progenitors had smaller apical domains compared with proliferative neuroepithelia. As nuclear position during interkinetic nuclear migration (IKNM) has been previously linked with cell cycle exit, we analyzed this phenomenon in cells depleted of Llgl1. We found that although IKNM was normal, the relationship between nuclear position and neurogenesis was shifted away from the apical surface, consistent with increased pro-proliferative and/or anti-neurogenic signals associated with the apical domain. These data, in conjunction with other findings, suggest that, in retinal neuroepithelia, the size of the apical domain modulates the strength of polarized signals that influence neurogenesis.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Clark
authors.forename: Shuang
authors.initials: S
authors.lastname: Cui
authors.forename: Joel B
authors.initials: JB
authors.lastname: Miesfeld
authors.forename: Olga
authors.initials: O
authors.lastname: Klezovitch
authors.forename: Valeri
authors.initials: V
authors.lastname: Vasioukhin
authors.forename: Brian A
authors.initials: BA
authors.lastname: Link
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D018797:Cell Cycle Proteins / Q000172:deficiency* / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009841:Oligonucleotides / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism*; D012160:Retina / Q000166:cytology*; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000378:metabolism / Q000502:physiology*; D029961:Zebrafish Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C572456:Llgl1 protein, zebrafish; D008840:Microfilament Proteins; D009841:Oligonucleotides; D051880:Receptors, Notch; D029961:Zebrafish Proteins; D001973:Bromodeoxyuridine