aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation

Niessen, Michaela; Scott, J. K.; Zielinski, Julia; Vorhagen, Susanne; Sotiropoulou, Panagiota A.; Blanpain, Cédric; Leitges, Michael; Niessen, Carien

doi:10.1083/jcb.201307001

Cited by 78 publications

(117 citation statements)

References 61 publications

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“…However, at P4, uniform/bipolar LGN was the predominant localization pattern in OE and headskin. This suggests that there might be a bias toward parallel divisions postnatally, as previously reported in backskin (Niessen et al, 2013) and tail epidermis (Clayton et al, 2007), although it has been reported that 85% of divisions in adult ear epidermis are perpendicular (Lechler and Fuchs, 2005). Similar patterns of LGN were observed at early ( prometaphase) and late (telophase) mitosis, in thin (8 µm) or thick (20 µm) sections ( Fig.…”

Section: Oral Epithelial Development Is Diverse and Dynamicsupporting

confidence: 60%

“…In epidermis and HFs lacking Prkcι, a ∼20% increase in perpendicular divisions is observed, leading to prolonged anagen, progressive loss of quiescent bulge HFSCs and, ultimately, hair loss (Niessen et al, 2013). It is presently unknown whether LGN directs these OCDs, although other proteins that colocalize with LGN, including Par3 and NuMA, appear to be expressed normally.…”

Section: Discussionmentioning

confidence: 99%

“…The functional importance of OCDs in postnatal HF morphogenesis has recently been shown through analysis of mice lacking Prkcι and NuMA (Niessen et al, 2013;Seldin et al, 2016). In epidermis and HFs lacking Prkcι, a ∼20% increase in perpendicular divisions is observed, leading to prolonged anagen, progressive loss of quiescent bulge HFSCs and, ultimately, hair loss (Niessen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Here we have examined one candidate and show a weaker concordance between LGN and Gαi3 in DT than in other regions. Other potential regulators of LGN cortical localization include Insc, the LGN homolog Ags3 (Gpsm1), Sapcd2, afadin (Mllt4), 4.1G/R (Epb41l2/ Epb41), 14-3-3 proteins, Par3 and aPKC (Prkcι) (Sanada and Tsai, 2005;Hao et al, 2010;Postiglione et al, 2011;Kiyomitsu and Cheeseman, 2013;Niessen et al, 2013;Seldin et al, 2013;Williams et al, 2014;Carminati et al, 2016;Chiu et al, 2016). Owing to the diverse patterns of LGN localization found in filiform papillae, we believe that the DT represents an ideal system with which to address this important question in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Recent work in the epidermis has shown that proper orientation of the mitotic spindle in basal epidermal progenitors is essential for skin development (Lechler and Fuchs, 2005;Poulson and Lechler, 2010;Williams et al, 2011Williams et al, , 2014Niessen et al, 2013). In stem cells, spindle orientation can influence cell fate choices, often by directing polarized inheritance of fate determinants that promote asymmetric cell divisions (Siller and Doe, 2009;Morin and Bellaiche, 2011;Lu and Johnston, 2013;Williams and Fuchs, 2013).…”

Section: Introductionmentioning

confidence: 99%

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LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

et al. 2016

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Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissuespecific functions in patterning surface ectoderm and its appendages by controlling division orientation.

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Section: Oral Epithelial Development Is Diverse and Dynamicsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

et al. 2016

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Influence of cell polarity on early development of the sea urchin embryo

Moorhouse

Gudejko

McDougall

et al. 2015

Developmental Dynamics

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Background Establishment and maintenance of cell polarity is critical for normal embryonic development. Previously, it was thought that the echinoderm embryo remained relatively unpolarized until the first asymmetric division at the 16 cell stage. Here we analyzed roles of the cell polarity regulators, the PAR complex proteins, and how their disruption in early development affects later developmental milestones. Results We found that PAR6, aPKC and CDC42 localize to the apical cortex as early as the 2 cell stage and that this localization is retained through the gastrula stage. Interestingly, PAR1 also colocalizes with these apical markers through the gastrula stage. Additionally, PAR1 was found to be in complex with aPKC, but not PAR6. PAR6, aPKC, and CDC42 are anchored in the cortical actin cytoskeleton by assembled myosin. Furthermore, assembled myosin was found to be necessary to maintain proper PAR6 localization through subsequent cleavage divisions. Interference with myosin assembly prevented the embryos from reaching the blastula stage, while transient disruptions of either actin or microtubules did not have this effect. Conclusions These observations suggest that disruptions of the polarity in the early embryo can have a significant impact on the ability of the embryo to reach later critical stages in development.

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How to be at the right place at the right time: The importance of spindle positioning in embryos

Moorhouse

Burgess

2014

Molecular Reproduction Devel

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SUMMARYSpindle positioning is an imperative cellular process that regulates a number of different developmental events throughout embryogenesis. The spindle must be properly positioned in embryos not only for the segregation of chromosomes, but also to segregate developmental determinants into different daughter blastomeres. In this review, the role of spindle positioning is explored in several different developmental model systems, which have revealed the diversity of factors that regulate spindle positioning. The C. elegans embryo, the Drosophila neuroblast, and ascidian embryos have all been utilized for the study of polarity-dependent spindle positioning, and exploration of the proteins that are required for asymmetric cell division. Work in the sea urchin embryo has examined the influence of cell shape and factors that affect secondary furrow formation. The issue of size scaling in extremely large cells, as well as the requirement for spindle positioning in developmental fate decisions in vertebrates, has been addressed by work in the Xenopus embryo. Further work in mouse oocytes has examined the roles of actin and myosin in spindle positioning. The data generated from these model organisms have made unique contributions to our knowledge of spindle positioning. Future work will address how all of these different factors work together to regulate the position of the spindle. Spindles play an important role in embryos as their location within the cell has a significant impact on subsequent development.

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aPKCλ controls epidermal homeostasis and stem cell fate through regulation of division orientation

Abstract: Loss of aPKCλ disrupts epidermal homeostasis and bulge stem cell maintenance by driving cell fate changes via a shift toward asymmetric division

Cited by 78 publications

References 61 publications

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

Influence of cell polarity on early development of the sea urchin embryo

How to be at the right place at the right time: The importance of spindle positioning in embryos

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