WNT-SHH Antagonism Specifies and Expands Stem Cells prior to Niche Formation

Ouspenskaia, Tamara; Matos, Irina; Mertz, Aaron F.; Fiore, Vincent F.; Fuchs, Elaine

doi:10.1016/j.cell.2015.11.058

Cited by 150 publications

(180 citation statements)

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“…9C,D). In agreement with Ouspenskaia et al (2016), we observed that all HP divisions were oriented perpendicular to the BM, while a typical bimodal distribution was seen in the IFE (Fig. 9E).…”

Section: Potential Upstream Regulators Of Differential Lgn Localizationsupporting

confidence: 87%

“…During embryogenesis, Lhx2 and Sox9 are among the earliest known transcription factors expressed in HPs, and are found in complementary patterns, with Lhx2 colocalizing with basal Pcad, and Sox9 positioned suprabasally (Rhee et al, 2006;Nowak et al, 2008 (Ouspenskaia et al, 2016). Genetic and lineage-tracing studies have shown that Sox9 + HFSCs specified during embryogenesis later take up residence in the bulge niche where they contribute to all postnatal HF lineages (Nowak et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…This Sox9 + population increases in number as HFs develop and is found in a pattern complementary to that of Pcad, which labels a quiescent population of Wnt hi /Shh + /Lhx2 + progenitors (Rhee et al, 2006;Nowak et al, 2008;Ouspenskaia et al, 2016). It was recently suggested that perpendicular asymmetric cell divisions in HPs help establish an asymmetry in Wnt and Shh responsiveness that specifies Sox9 + progenitors (Ouspenskaia et al, 2016). To address whether LGN is required for the specification of Sox9 + progenitors, we examined the position and number of Sox9 + cells at different stages of HF morphogenesis.…”

Section: Potential Upstream Regulators Of Differential Lgn Localizationmentioning

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: Potential Upstream Regulators Of Differential Lgn Localizationsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Potential Upstream Regulators Of Differential Lgn Localizationmentioning

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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“…These results correlated with GO-term analyses of WNT- Our data on FGFs further bolstered the importance of mesenchymal-to-epithelial signaling circuits for Shh suppression in foot skin. That said, Wnt signaling is required and upstream of Shh expression in hair buds (20,21) and is repressed in SwG buds (Fig. 4A and fig.…”

Section: All Roads Lead To Suppression Of Shh Signaling In Swg-permismentioning

confidence: 94%

“…That said, Wnt signaling is required and upstream of Shh expression in hair buds (20,21) and is repressed in SwG buds (Fig. 4A and fig.…”

Section: All Roads Lead To Suppression Of Shh Signaling In Swg-permismentioning

confidence: 99%

839 Spatiotemporal antagonism in mesenchymal-epithelial Signaling in sweat versus hair fate decision

Polak

Keyes

et al. 2017

Journal of Investigative Dermatology

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The gain of eccrine sweat glands in hairy body skin has empowered humans to run marathons and tolerate temperature extremes. Epithelial-mesenchymal cross-talk is integral to the diverse patterning of skin appendages, but the molecular events underlying their specification remain largely unknown. Using genome-wide analyses and functional studies, we show that sweat glands are specified by mesenchymal-derived bone morphogenetic proteins (BMPs) and fibroblast growth factors that signal to epithelial buds and suppress epithelial-derived sonic hedgehog (SHH) production. Conversely, hair follicles are specified when mesenchymal BMP signaling is blocked, permitting SHH production. Fate determination is confined to a critical developmental window and is regionally specified in mice. In contrast, a shift from hair to gland fates is achieved in humans when a spike in BMP silences SHH during the final embryonic wave(s) of bud morphogenesis.Epithelial appendages-including hair follicles (HFs) and teeth as well as mammary, sweat, and salivary glands-begin to form during embryogenesis when Wnt signaling triggers progenitors within the epithelial sheet to organize spatially into morphologically similar placodes. Whereas most mammals restrict the specification of epidermal appendages regionally, HFs and sweat glands (SwGs) coexist throughout much of the skin of primates. The acquisition of SwGs and their importance in thermoregulation are underscored by humans who suffer from a life-threatening condition when SwGs are eliminated, either from loss in severe burns or from the genetic disorder hypohidrotic ectodermal dysplasia (HED).Patients with HED display mutations in genes encoding proteins such as ectodermal dysplasia antigen (EDA), the EDA receptor (EDAR), and WNT10a, a ligand for Wnt signaling. These findings have illuminated a critical role for these pathways in controlling the development of a number of epidermal appendages, including SwGs and coarse hairs (1, † Corresponding author. fuchslb@rockefeller.edu. * Present address: Calico Life Sciences, South San Francisco, CA 94080, USA.RNAseq data are deposited in the Gene Expression Omnibus under accession number GSE85249 (www.ncbi.nlm.nih.gov/geo).The authors declare no competing financial interests. SUPPLEMENTARY MATERIALS Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript 2). Conversely, an EDAR gain-of-function variant has been expanding among the Southeast Asian population, where excessive SwGs are desirable because of the hot and humid climate of that region (3). In this regard, both Wnt and EDA/EDAR pathways appear to function in promoting placode formation, increasing the density of SwGs and several other appendage types (4).Classical tissue recombination experiments have revealed that mesenchyme plays a critical role in dictating the divergent downstream events that determine appendage selection (5, 6). For example, salivary mesenchyme combined with mammary epithelium generates an epithelial morphology resembling salivary glands (7), and...

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Vertebrate Embryo: Development of the Skin and Its Appendages

Lei

Inaba

Chuong

2016

Encyclopedia of Life Sciences

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Vertebrate skin consists of epidermis and dermis, both of which are characterised as highly heterogeneous suborgan/tissues containing complex structures with diverse functions. Skin epidermis starts to stratify during embryogenesis. It plays pivotal barrier functions in protecting the organism from water loss and environmental insults during postnatal life. The dermis is a connective tissue that is separated with the epidermis by a deposition of extracellular matrix called the basement membrane. During skin development, many skin appendages are also induced. Those include epidermal appendages such as feather follicles, hair follicles, sebaceous glands and sweat glands and dermal appendages such as the arrector pili muscle. More and more stem cell populations are characterised in these appendages recently. In addition, considerable progress has been made in identifying molecules and pathways that regulate development and regeneration of skin and its appendages. Key Concepts During chick skin development, feathered areas are formed in the skin with high‐cell density of dermal cells and naked areas are formed in low‐cell density regions. Feather and hair development begins from thickening of epidermis and condensation of dermal cells, which is associated with the interaction among morphogens such as FGFs and BMPs. The mechanism by which feather buds are arranged in a periodic pattern on the skin and branching formation within each bud might be explained by reaction–diffusion model, one of the mathematical models. Feather follicles are differentiated from feather buds with the invaginated epidermis and the feathers have an ability of regeneration throughout lifetime owing to feather stem cells. Development and regeneration of hair follicle involve reciprocal epidermal and dermal cell interactions. Sequential activation of molecules including Wnt‐Eda‐Shh et al. is required for hair follicle development. Secondary hair germ cells first response, followed by bulge stem cell activation during hair regeneration. Regenerative hair cycling is regulated by epigenetic, microenvironment and macroenvironment factors.

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WNT-SHH Antagonism Specifies and Expands Stem Cells prior to Niche Formation

Cited by 150 publications

References 56 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

839 Spatiotemporal antagonism in mesenchymal-epithelial Signaling in sweat versus hair fate decision

Vertebrate Embryo: Development of the Skin and Its Appendages

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