RESEARCH HIGHLIGHTS Nature Reviews Molecular Cell Biology | AOP, published online 30 October 2013; doi:10.1038/nrm3697
CELL DIVISION
Ciliary membrane inheritance directs ciliogenesis
the shortening cilium is internalized with the mother centriole prior to mitosis
Primary cilia are microtubule-based sensory organelles that are surrounded by a ciliary membrane. They are nucleated at their base by the mother centriole, and an accepted model is that primary cilia are disassembled prior to mitosis so that the centrosomes can function at mitotic spindle poles. Paridaen et al. investigated the fate of the ciliary membrane following cell division and now report the unexpected finding that it remains attached to the mother centriole at one spindle pole throughout mitosis. As a result, the membrane is only inherited by one daughter cell, which leads to the asymmetric re-establishment of the cilium and ciliary signalling in daughter cells. The authors found that in mitotic mouse apical progenitor cells (which are epithelial neural stem cells), the GTPase ADP-ribosylation factor-like protein 13B (ARL13B; which marks
NPG
the primary cilium membrane) localized to the mother centriolecontaining centrosome throughout mitosis. Using electron microscopy, they showed that the centriole was attached to membranous structures. These structures corresponded to the ARL13B-positive puncta seen by light microscopy, which suggests that they were remnants of the ciliary membrane. In agreement with this idea, enhanced GFP-tagged ciliary membrane proteins were detected in close proximity to centro somes in mitotic apical progenitor cells. Further work showed that centrosome-associated ARL13Bpositive membrane is endocytosed from the cell surface at the onset of mitosis, and thus that the primary cilium is not completely disassembled prior to mitosis but instead that a ciliary remnant remains attached to the mother centriole. Next, the authors monitored dividing apical progenitor cells and their progeny and found that the ciliary remnant was asymmetrically inherited — that is, by only one daughter cell. Importantly, the daughter cell that inherited this ciliary remnant reformed a cilium earlier than its sister cell, which could only reform the cilium after the new mother centriole (that is, the previous daughter centriole) had docked to the lateral membrane to nucleate a cilium de novo. Previous studies suggested that asynchronous cilium reassembly is linked to differential ciliary signalling between daughter cells, and the authors asked whether asymmetric ciliary remnant inheritance has
NATURE REVIEWS | MOLECULAR CELL BIOLOGY
a role in this phenomenon. They found that the ciliary accumulation of activated Smoothened (SMO; a membrane protein that transduces sonic hedgehog (SHH) signalling), and thus the activation of SHH signal transduction, occurred earlier in cells that inherited the ciliary remnant than in their sister cells. Finally, mitotic apical progenitor cells are known to asymmetrically distribute their basal process (a structure implicated in the self-renewal of neural stem cells) to the daughter cells. Importantly, most cells that inherited the basal process, and thus that maintained the stem cell character, also inherited the ciliary membrane. Together, these data show that the shortening cilium is internalized with the mother centriole prior to mitosis, which challenges the model that it is completely disassembled. This study uncovers a new pathway of ciliogenesis whereby one daughter cell (preferentially the stem cell daughter cell) inherits the ciliary membrane-containing centriole and directly proceeds with cilium outgrowth and early ciliary signalling. In addition, centrosomal attachment of the ciliary membrane decreased at late neurogenesis. Therefore, asymmetric ciliary membrane inheritance spatio‑temporarily controls ciliogenesis. Andrea Du Toit ORIGINAL RESEARCH PAPER Paridaen, J. T. M. L., Wilsch-Bräuninger, M. & Huttner, W. B. Asymmetric inheritance of centrosome-associated primary cilium membrane directs ciliogenesis after cell division. Cell 155, 333–344 (2013)
VOLUME 14 | DECEMBER 2013 © 2013 Macmillan Publishers Limited. All rights reserved
CELL DIVISION
Ciliary membrane inheritance directs ciliogenesis
the shortening cilium is internalized with the mother centriole prior to mitosis
Primary cilia are microtubule-based sensory organelles that are surrounded by a ciliary membrane. They are nucleated at their base by the mother centriole, and an accepted model is that primary cilia are disassembled prior to mitosis so that the centrosomes can function at mitotic spindle poles. Paridaen et al. investigated the fate of the ciliary membrane following cell division and now report the unexpected finding that it remains attached to the mother centriole at one spindle pole throughout mitosis. As a result, the membrane is only inherited by one daughter cell, which leads to the asymmetric re-establishment of the cilium and ciliary signalling in daughter cells. The authors found that in mitotic mouse apical progenitor cells (which are epithelial neural stem cells), the GTPase ADP-ribosylation factor-like protein 13B (ARL13B; which marks
NPG
the primary cilium membrane) localized to the mother centriolecontaining centrosome throughout mitosis. Using electron microscopy, they showed that the centriole was attached to membranous structures. These structures corresponded to the ARL13B-positive puncta seen by light microscopy, which suggests that they were remnants of the ciliary membrane. In agreement with this idea, enhanced GFP-tagged ciliary membrane proteins were detected in close proximity to centro somes in mitotic apical progenitor cells. Further work showed that centrosome-associated ARL13Bpositive membrane is endocytosed from the cell surface at the onset of mitosis, and thus that the primary cilium is not completely disassembled prior to mitosis but instead that a ciliary remnant remains attached to the mother centriole. Next, the authors monitored dividing apical progenitor cells and their progeny and found that the ciliary remnant was asymmetrically inherited — that is, by only one daughter cell. Importantly, the daughter cell that inherited this ciliary remnant reformed a cilium earlier than its sister cell, which could only reform the cilium after the new mother centriole (that is, the previous daughter centriole) had docked to the lateral membrane to nucleate a cilium de novo. Previous studies suggested that asynchronous cilium reassembly is linked to differential ciliary signalling between daughter cells, and the authors asked whether asymmetric ciliary remnant inheritance has
NATURE REVIEWS | MOLECULAR CELL BIOLOGY
a role in this phenomenon. They found that the ciliary accumulation of activated Smoothened (SMO; a membrane protein that transduces sonic hedgehog (SHH) signalling), and thus the activation of SHH signal transduction, occurred earlier in cells that inherited the ciliary remnant than in their sister cells. Finally, mitotic apical progenitor cells are known to asymmetrically distribute their basal process (a structure implicated in the self-renewal of neural stem cells) to the daughter cells. Importantly, most cells that inherited the basal process, and thus that maintained the stem cell character, also inherited the ciliary membrane. Together, these data show that the shortening cilium is internalized with the mother centriole prior to mitosis, which challenges the model that it is completely disassembled. This study uncovers a new pathway of ciliogenesis whereby one daughter cell (preferentially the stem cell daughter cell) inherits the ciliary membrane-containing centriole and directly proceeds with cilium outgrowth and early ciliary signalling. In addition, centrosomal attachment of the ciliary membrane decreased at late neurogenesis. Therefore, asymmetric ciliary membrane inheritance spatio‑temporarily controls ciliogenesis. Andrea Du Toit ORIGINAL RESEARCH PAPER Paridaen, J. T. M. L., Wilsch-Bräuninger, M. & Huttner, W. B. Asymmetric inheritance of centrosome-associated primary cilium membrane directs ciliogenesis after cell division. Cell 155, 333–344 (2013)
VOLUME 14 | DECEMBER 2013 © 2013 Macmillan Publishers Limited. All rights reserved
