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Ye Tian - One of the best experts on this subject based on the ideXlab platform.
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fam20b catalyzed glycosaminoglycans control murine Tooth Number by restricting fgfr2b signaling
BMC Biology, 2020Co-Authors: Ye Tian, Lu Han, Chao Liu, Tianyu Sun, Bikash Lamichhane, Rena N DsouzaAbstract:The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary Tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary Tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine Tooth Number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of Tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary Tooth formation. The novel mechanism we have characterized through which GAGs control the Tooth Number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis.
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FAM20B-catalyzed glycosaminoglycans control murine Tooth Number by restricting FGFR2b signaling.
eScholarship University of California, 2020Co-Authors: Wu Jingyi, Ye Tian, Lu Han, Liu Chao, Sun Tianyu, Li Ling, Yu Yanlei, Lamichhane Bikash, D'souza, Rena N, Millar, Sarah EAbstract:BACKGROUND:The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary Tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. RESULTS:In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary Tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine Tooth Number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of Tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary Tooth formation. CONCLUSIONS:The novel mechanism we have characterized through which GAGs control the Tooth Number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis
Lu Han - One of the best experts on this subject based on the ideXlab platform.
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fam20b catalyzed glycosaminoglycans control murine Tooth Number by restricting fgfr2b signaling
BMC Biology, 2020Co-Authors: Ye Tian, Lu Han, Chao Liu, Tianyu Sun, Bikash Lamichhane, Rena N DsouzaAbstract:The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary Tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary Tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine Tooth Number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of Tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary Tooth formation. The novel mechanism we have characterized through which GAGs control the Tooth Number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis.
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FAM20B-catalyzed glycosaminoglycans control murine Tooth Number by restricting FGFR2b signaling.
eScholarship University of California, 2020Co-Authors: Wu Jingyi, Ye Tian, Lu Han, Liu Chao, Sun Tianyu, Li Ling, Yu Yanlei, Lamichhane Bikash, D'souza, Rena N, Millar, Sarah EAbstract:BACKGROUND:The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary Tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. RESULTS:In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary Tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine Tooth Number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of Tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary Tooth formation. CONCLUSIONS:The novel mechanism we have characterized through which GAGs control the Tooth Number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis
Rena N Dsouza - One of the best experts on this subject based on the ideXlab platform.
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fam20b catalyzed glycosaminoglycans control murine Tooth Number by restricting fgfr2b signaling
BMC Biology, 2020Co-Authors: Ye Tian, Lu Han, Chao Liu, Tianyu Sun, Bikash Lamichhane, Rena N DsouzaAbstract:The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary Tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary Tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine Tooth Number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of Tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary Tooth formation. The novel mechanism we have characterized through which GAGs control the Tooth Number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis.
Craig T Miller - One of the best experts on this subject based on the ideXlab platform.
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genetic dissection of a supergene implicates tfap2a in craniofacial evolution of threespine sticklebacks
Genetics, 2018Co-Authors: Priscilla A Erickson, Jiyeon Baek, James C Hart, Phillip A Cleves, Craig T MillerAbstract:In nature, multiple adaptive phenotypes often coevolve and can be controlled by tightly linked genetic loci known as supergenes. Dissecting the genetic basis of these linked phenotypes is a major challenge in evolutionary genetics. Multiple freshwater populations of threespine stickleback fish (Gasterosteus aculeatus) have convergently evolved two constructive craniofacial traits, longer branchial bones and increased pharyngeal Tooth Number, likely as adaptations to dietary differences between marine and freshwater environments. Prior QTL mapping showed that both traits are partially controlled by overlapping genomic regions on chromosome 21 and that a regulatory change in Bmp6 likely underlies the Tooth Number QTL. Here, we mapped the branchial bone length QTL to a 155 kb, eight-gene interval tightly linked to, but excluding the coding regions of Bmp6 and containing the candidate gene Tfap2a Further recombinant mapping revealed this bone length QTL is separable into at least two loci. During embryonic and larval development, Tfap2a was expressed in the branchial bone primordia, where allele specific expression assays revealed the freshwater allele of Tfap2a was expressed at lower levels relative to the marine allele in hybrid fish. Induced loss-of-function mutations in Tfap2a revealed an essential role in stickleback craniofacial development and show that bone length is sensitive to Tfap2a dosage in heterozygotes. Combined, these results suggest that closely linked but genetically separable changes in Bmp6 and Tfap2a contribute to a supergene underlying evolved skeletal gain in multiple freshwater stickleback populations.
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Bmp6 is required for viability, growth, and Tooth patterning.
2018Co-Authors: Phillip A Cleves, Priscilla A Erickson, James C Hart, Rachel M. Agoglia, Monica T. Jimenez, Linda Gai, Craig T MillerAbstract:(A) Schematic of TALEN pair (green) targeting an EcoRI site (asterisk) in the second exon of Bmp6. (B) Sanger sequencing of F0 or F1 fish revealed a spectrum of genomic deletions (colons) and insertions (red) in Bmp6. The two mutations used in this study are in bold. In the wild-type sequence, the EcoRI site is shown in blue and the edges of the TALEN targeting sequences shown in green. (C) Confocal images of early juvenile (16–17 mm total length) wild-type (left) and homozygous mutant (right) ventral pharyngeal Tooth plates showing fewer teeth in mutant. Mutant shown is transheterozygote for 13 bp deletion and 3 bp deletion+4 bp insertion. Scale bar is 200 μm. (D-F) Developmental time course of Tooth Number (D), Tooth plate area (E), and Tooth spacing (F) in wild-type (blue), heterozygous (purple), and homozygous mutant (red) fish. (D-E) Homozygous fish have recessive reduction of Tooth Number and Tooth plate area at the early juvenile stage (Tukey post-hoc P values comparing wild-type to homozygous mutant are 9.3 x10-6 and 0.004, respectively and comparing heterozygous to homozygous mutant are 1.3x10-4 and 0.08, respectively). Tooth Number and area diverges late in development between wild-type and heterozygous fish. (F) Tooth spacing is not significantly different in the mutant at any stage. The late juvenile and adult crosses were heterozygous mutant backcrossed to wild-type fish. For D-F, homozygous mutants include both fish homozygous for the 13 bp deletion mutation and fish transheterozygous for the 13 bp deletion and the 3 bp deletion + 4 bp insertion (see S7 Table and S1 File Source Data File).
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An intronic enhancer of Bmp6 underlies evolved Tooth gain in sticklebacks
2018Co-Authors: Phillip A Cleves, Priscilla A Erickson, James C Hart, Rachel M. Agoglia, Monica T. Jimenez, Linda Gai, Craig T MillerAbstract:Threespine stickleback fish offer a powerful system to dissect the genetic basis of morphological evolution in nature. Marine sticklebacks have repeatedly invaded and adapted to numerous freshwater environments throughout the Northern hemisphere. In response to new diets in freshwater habitats, changes in craniofacial morphology, including heritable increases in Tooth Number, have evolved in derived freshwater populations. Using a combination of quantitative genetics and genome resequencing, here we fine-mapped a quantitative trait locus (QTL) regulating evolved Tooth gain to a cluster of ten QTL-associated single nucleotide variants, all within intron four of Bone Morphogenetic Protein 6 (Bmp6). Transgenic reporter assays revealed this intronic region contains a Tooth enhancer. We induced mutations in Bmp6, revealing required roles for survival, growth, and Tooth patterning. Transcriptional profiling of Bmp6 mutant dental tissues identified significant downregulation of a set of genes whose orthologs were previously shown to be expressed in quiescent mouse hair stem cells. Collectively these data support a model where mutations within a Bmp6 intronic Tooth enhancer contribute to evolved Tooth gain, and suggest that ancient shared genetic circuitry regulates the regeneration of diverse vertebrate epithelial appendages including mammalian hair and fish teeth.
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distinct developmental genetic mechanisms underlie convergently evolved Tooth gain in sticklebacks
Development, 2015Co-Authors: Nicholas A Ellis, Phillip A Cleves, Rachel M. Agoglia, Andrew M Glazer, Nikunj N Donde, Craig T MillerAbstract:Teeth are a classic model system of organogenesis, as repeated and reciprocal epithelial and mesenchymal interactions pattern placode formation and outgrowth. Less is known about the developmental and genetic bases of Tooth formation and replacement in polyphyodonts, which are vertebrates with continual Tooth replacement. Here, we leverage natural variation in the threespine stickleback fish Gasterosteus aculeatus to investigate the genetic basis of Tooth development and replacement. We find that two derived freshwater stickleback populations have both convergently evolved more ventral pharyngeal teeth through heritable genetic changes. In both populations, evolved Tooth gain manifests late in development. Using pulse-chase vital dye labeling to mark newly forming teeth in adult fish, we find that both high-Toothed freshwater populations have accelerated Tooth replacement rates relative to low-Toothed ancestral marine fish. Despite the similar evolved phenotype of more teeth and an accelerated adult replacement rate, the timing of Tooth Number divergence and the spatial patterns of newly formed adult teeth are different in the two populations, suggesting distinct developmental mechanisms. Using genome-wide linkage mapping in marine-freshwater F2 genetic crosses, we find that the genetic basis of evolved Tooth gain in the two freshwater populations is largely distinct. Together, our results support a model whereby increased Tooth Number and an accelerated Tooth replacement rate have evolved convergently in two independently derived freshwater stickleback populations using largely distinct developmental and genetic mechanisms.
Chao Liu - One of the best experts on this subject based on the ideXlab platform.
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fam20b catalyzed glycosaminoglycans control murine Tooth Number by restricting fgfr2b signaling
BMC Biology, 2020Co-Authors: Ye Tian, Lu Han, Chao Liu, Tianyu Sun, Bikash Lamichhane, Rena N DsouzaAbstract:The formation of supernumerary teeth is an excellent model for studying the molecular mechanisms that control stem/progenitor cell homeostasis needed to generate a renewable source of replacement cells and tissues. Although multiple growth factors and transcriptional factors have been associated with supernumerary Tooth formation, the regulatory inputs of extracellular matrix in this regenerative process remains poorly understood. In this study, we present evidence that disrupting glycosaminoglycans (GAGs) in the dental epithelium of mice by inactivating FAM20B, a xylose kinase essential for GAG assembly, leads to supernumerary Tooth formation in a pattern reminiscent of replacement teeth. The dental epithelial GAGs confine murine Tooth Number by restricting the homeostasis of Sox2(+) dental epithelial stem/progenitor cells in a non-autonomous manner. FAM20B-catalyzed GAGs regulate the cell fate of dental lamina by restricting FGFR2b signaling at the initial stage of Tooth development to maintain a subtle balance between the renewal and differentiation of Sox2(+) cells. At the later cap stage, WNT signaling functions as a relay cue to facilitate the supernumerary Tooth formation. The novel mechanism we have characterized through which GAGs control the Tooth Number in mice may also be more broadly relevant for potentiating signaling interactions in other tissues during development and tissue homeostasis.
