Figure 7

Proposed model for relationship of Nuclear Position, endosome activity, and the regulation of polarized signaling and retinal neurogenesis. Model figure suggesting the functional significance of nuclear position in the regulation of apical endosome concentration, Rab11a recycling endosome activity, the regulation of Crb2a apical protein localization and the regulation of autonomous signaling. In cells with apical nuclei (A) we suggest apical concentration of Rab11a-positive recycling endosomes biases a state in which Rab11a is preferentially in the inactive, GDP-bound form, due to the close proximity of apical recycling endosomes to the centrosome-localized Rab11a-GAP, Evi5b. This in turn decreases recycling of Crb2a to the apical junctions, thereby decreasing the cis-inhibition of Notch signaling by Crb2a (increased Notch signaling) and mis-localizing Crb2a interacting proteins from the apical junction. Combined these changes promote autonomous signaling to promote a proliferative state. In cells with basal nuclei (B) Rab11a is preferentially in a GTP-bound active state, promoting Crb2a recycling, inhibiting Notch-signaling, and maintaining apical localization of Crb2a-interacting proteins. In combination, this biases cells toward an autonomous signaling state that promotes neurogenesis. AJ, Apical Junctions.