Clark, B.S., Cui, S., Miesfeld, J.B., Klezovitch, O., Vasioukhin, V., and Link, B.A. (2012) Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis. Development (Cambridge, England). 139(9):1599-1610.
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.