Date Published: January 17, 2017
Publisher: Public Library of Science
Author(s): Christina B. Wölwer, Nathan Gödde, Luke B. Pase, Imogen A. Elsum, Krystle Y. B. Lim, Faruk Sacirbegovic, Carl R. Walkley, Sarah Ellis, Shigeo Ohno, Fumio Matsuzaki, Sarah M. Russell, Patrick O. Humbert, Hongyan Wang.
Erythroid enucleation is the process by which the future red blood cell disposes of its nucleus prior to entering the blood stream. This key event during red blood cell development has been likened to an asymmetric cell division (ACD), by which the enucleating erythroblast divides into two very different daughter cells of alternate molecular composition, a nucleated cell that will be removed by associated macrophages, and the reticulocyte that will mature to the definitive erythrocyte. Here we investigated gene expression of members of the Par, Scribble and Pins/Gpsm2 asymmetric cell division complexes in erythroid cells, and functionally tested their role in erythroid enucleation in vivo and ex vivo. Despite their roles in regulating ACD in other contexts, we found that these polarity regulators are not essential for erythroid enucleation, nor for erythroid development in vivo. Together our results put into question a role for cell polarity and asymmetric cell division in erythroid enucleation.
Erythroid enucleation embodies many features of an asymmetric cell division[1–10] and results in the generation of two unique daughter cells: the pyrenocyte containing the condensed nucleus and the anucleated reticulocyte that will further mature into the erythrocyte found in the peripheral blood. One of the first visible steps of establishing polarity prior to nuclear extrusion is the phosphoinositide 3-kinase/microtubule -directed migration of the nucleus to one side of the cytoplasm, whereby the nucleus apposes the cell membrane. This event is followed by a polarized enrichment of cytoskeletal elements, including actin, and myosin II to the future restriction site between pyrenocyte and future red blood cell[6–9]. During the enucleation process specific membrane proteins are either sorted to the nucleus (e.g. Emp protein) or to the future reticulocyte (e.g. spectrin)[7, 10].