Dataset Information

Homeobox code model of heterodont tooth in mammals revised.

ABSTRACT: Heterodonty is one of the hallmarks of mammals. It has been suggested that, homeobox genes, differentially expressed in the ectomesenchyme of the jaw primordium along the distal-proximal axis, would determine the tooth classes (homeobox code model) based on mouse studies. Because mouse has highly specialized tooth pattern lacking canine and premolars (dental formula: 1003/1003, for upper and lower jaws, respectively), it is unclear if the suggested model could be applied for mammals with all tooth classes, including human. We thus compared the homeobox code gene expressions in various mammals, such as opossum (5134/4134), ferret (3131/3132), as well as mouse. We found that Msx1 and BarX1 expression domains in the jaw primordium of the opossum and ferret embryos show a large overlap, but such overlap is small in mouse. Detailed analyses of gene expressions and subsequent morphogenesis of tooth germ in the opossum indicated that the Msx1/BarX1 double-positive domain will correspond to the premolar region, and Alx3-negative/Msx1-positive/BarX1-negative domain will correspond to canine. This study therefore provides a significant update of the homeobox code model in the mammalian heterodonty. We also show that the modulation of FGF-mediated Msx1 activation contributes to the variation in the proximal Msx1 expression among species.

SUBMITTER: Wakamatsu Y

PROVIDER: S-EPMC6731288 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Homeobox code model of heterodont tooth in mammals revised.

Wakamatsu Yoshio Y Egawa Shiro S Terashita Yukari Y Kawasaki Hiroshi H Tamura Koji K Suzuki Kunihiro K

Scientific reports 20190906 1

Heterodonty is one of the hallmarks of mammals. It has been suggested that, homeobox genes, differentially expressed in the ectomesenchyme of the jaw primordium along the distal-proximal axis, would determine the tooth classes (homeobox code model) based on mouse studies. Because mouse has highly specialized tooth pattern lacking canine and premolars (dental formula: 1003/1003, for upper and lower jaws, respectively), it is unclear if the suggested model could be applied for mammals with all too ...[more]

PMID: 31492950

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Project description:Homeobox genes encode transcription factors which regulate basic processes in development and cell differentiation and are grouped into classes and subclasses according to sequence similarities. Here, we analyzed the activities of the 20 members strong TALE homeobox gene class in early hematopoiesis and in lymphopoiesis including developing and mature B-cells, T-cells, natural killer (NK)-cells and innate lymphoid cells (ILC). The resultant expression pattern comprised eleven genes and which we termed TALE-code enables discrimination of normal and aberrant activities of TALE homeobox genes in lymphoid malignancies. Subsequent expression analysis of TALE homeobox genes in public datasets of Hodgkin lymphoma (HL) patients revealed overexpression of IRX3, IRX4, MEIS1, MEIS3, PBX1, PBX4 and TGIF1. As paradigm we focused on PBX1 which was deregulated in about 17% HL patients. Normal PBX1 expression was restricted to hematopoietic stem cells and progenitors of T-cells and ILCs but absent in B-cells, reflecting its roles in stemness and early differentiation. HL cell line SUP-HD1 expressed enhanced PBX1 levels and served as an in vitro model to identify upstream regulators and downstream targets in this malignancy. Genomic studies of this cell line therein showed a gain of the PBX1 locus at 1q23 which may underlie its aberrant expression. Comparative expression profiling analyses of HL patients and cell lines followed by knockdown experiments revealed NFIB and TLX2 as target genes activated by PBX1. HOX proteins operate as cofactors of PBX1. Accordingly, our data showed that HOXB9 overexpressed in HL coactivated TLX2 but not NFIB while activating TNFRSF9 without PBX1. Further downstream analyses showed that TLX2 activated TBX15 which operated anti-apoptotically. Taken together, we discovered a lymphoid TALE-code and identified an aberrant network around deregulated TALE homeobox gene PBX1 which may disturb B-cell differentiation in HL by reactivation of progenitor-specific genes. These findings may provide the framework for future studies to exploit possible vulnerabilities of malignant cells in therapeutic scenarios.

Dataset Information

Homeobox code model of heterodont tooth in mammals revised.

Publications

Homeobox code model of heterodont tooth in mammals revised.

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