Spindle orientation processes in epithelial growth and organisation

Panousopoulou, Eleni; Green, Jeremy

doi:10.1016/j.semcdb.2014.06.013

Cited by 12 publications

(8 citation statements)

References 95 publications

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“…The orientation of cell division is carefully controlled in both embryonic and adult tissues, in which it may regulate cell fate, generate tissue shape, and maintain normal histological architecture [1][2][3]. Studies conducted over the last two decades have established that this process may play an important role to regulate the delicate balance between proliferation and differentiation that underlies normal brain development, with particular regard to the generation of a normal number of cortical neurons [2,4,5].…”

Section: Introductionmentioning

confidence: 99%

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules

et al. 2016

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Correct orientation of cell division is considered an important factor for the achievement of normal brain size, as mutations in genes that affect this process are among the leading causes of microcephaly. Abnormal spindle orientation is associated with reduction of the neuronal progenitor symmetric divisions, premature cell cycle exit, and reduced neurogenesis. This mechanism has been involved in microcephaly resulting from mutation of ASPM, the most frequently affected gene in autosomal recessive human primary microcephaly (MCPH), but it is presently unknown how ASPM regulates spindle orientation. In this report, we show that ASPM may control spindle positioning by interacting with citron kinase (CITK), a protein whose loss is also responsible for severe microcephaly in mammals. We show that the absence of CITK leads to abnormal spindle orientation in mammals and insects. In mouse cortical development, this phenotype correlates with increased production of basal progenitors. ASPM is required to recruit CITK at the spindle, and CITK overexpression rescues ASPM phenotype. ASPM and CITK affect the organization of astral microtubules (MT), and low doses of MT-stabilizing drug revert the spindle orientation phenotype produced by their knockdown. Finally, CITK regulates both astral-MT nucleation and stability. Our results provide a functional link between two established microcephaly proteins.

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Section: Introductionmentioning

confidence: 99%

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules

et al. 2016

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“…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). In developing epidermis, division orientation undergoes dynamic changes during stratification and has been linked to cell fate choices, such that planar divisions are thought to be symmetric whereas perpendicular divisions are asymmetric (Poulson and Lechler, 2010;Williams et al, 2011Williams et al, , 2014Panousopoulou and Green, 2014). Initially, most basal cells divide with the mitotic spindle parallel to the basement membrane (BM), but as the epidermis begins to stratify oblique and perpendicular divisions become more numerous and by E16 ∼60% of divisions are perpendicular (Smart, 1970;Byrne et al, 1994;Lechler and Fuchs, 2005;Williams et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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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“…Punctate BrdU retention could indicate greater dilution of the initial incorporation due to replication. In addition to proliferation, changes in the orientation of cell division have been shown to lead to changes in the shape of developing organs ( Economou et al, 2013 ; Panousopoulou and Green, 2014 ). We therefore assessed the orientation of mitotic figures in anaphase in the molar tail, focusing on couples of segregated chromosomes located in the basal-suprabasal epithelium ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Epithelial topography for repetitive tooth formation

et al. 2015

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During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells.

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Spindle orientation processes in epithelial growth and organisation

Cited by 12 publications

References 95 publications

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules

ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules

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

Epithelial topography for repetitive tooth formation

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