Ift88 regulates enamel formation via involving Shh signaling.

Objectives: The ciliopathies are a wide spectrum of human diseases, which are caused by perturbations in the function of primary cilia. Tooth enamel anomalies are often seen in ciliopathy patients; however, the role of primary cilia in enamel formation remains unclear.

Materials And Methods: We examined mice with epithelial conditional deletion of the ciliary protein, Ift88, (Ift88 ;K14Cre).

Expression of R-spondins/Lgrs in development of movable craniofacial organs.

Wnt signaling plays a critical role in the development of many organs, including the major movable craniofacial organs tongue, lip, and eyelid. Four members of the R-spondin family (Rspo1-4) bind to Lgr4/5/6 to regulate the activation of Wnt signaling. However, it is not fully understood how Rspos/Lgrs regulate Wnt signaling during the development of movable craniofacial organs.

MicroRNAs regulate distal region of mandibular development through Hh signaling.

Mandibular anomalies are often seen in various congenital diseases, indicating that mandibular development is under strict molecular control. Therefore, it is crucial to understand the molecular mechanisms involved in mandibular development. MicroRNAs (miRNAs) are noncoding small single-stranded RNAs that play a critical role in regulating the level of gene expression.

Overactivation of the NF-κB pathway impairs molar enamel formation.

Objective: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder characterized by abnormal structures and functions of the ectoderm-derived organs, including teeth. HED patients exhibit a variety of dental symptoms, such as hypodontia. Although disruption of the EDA/EDAR/EDARADD/NF-κB pathway is known to be responsible for HED, it remains unclear whether this pathway is involved in the process of enamel formation.

Molecular mechanisms in palatal rugae development.

Background: Periodic patterning of iterative structures is diverse across the animal kingdom. Clarifying the molecular mechanisms involved in the formation of these structures helps to elucidate the genetic commonality of developmental processes, as organs with these structures are believed to share the same molecular mechanisms and fundamental processes. Palatal rugae are periodic corrugated structures on the hard palate and are conserved in all mammals.

Ift88 is involved in mandibular development.

The mandible is a crucial organ in both clinical and biological fields due to the high frequency of congenital anomalies and the significant morphological changes during evolution. Primary cilia play a critical role in many biological processes, including the determination of left/right axis patterning, the regulation of signaling pathways, and the formation of bone and cartilage. Perturbations in the function of primary cilia are known to cause a wide spectrum of human diseases: the ciliopathies.

Primary cilia in murine palatal rugae development.

Periodic patterning of iterative structures is a fundamental process during embryonic development, since these structures are diverse across the animal kingdom. Therefore, elucidating the molecular mechanisms in the formation of these structures promotes understanding of the process of organogenesis. Periodically patterned ridges, palatal rugae (situated on the hard palate of mammals), are an excellent experimental model to clarify the molecular mechanisms involved in the formation of periodic patterning of iterative structures.

Bmp signaling in molar cusp formation.

Tooth cusp is a crucial structure, since the shape of the molar tooth is determined by number, shape, and size of the cusp. Bone morphogenetic protein (Bmp) signaling is known to play a critical role in tooth development, including in initiation. However, it remains unclear whether Bmp signaling is also involved in cusp formation.

Ift88 limits bone formation in maxillary process through suppressing apoptosis.

Objective: The development of the maxillary bone is under strict molecular control because of its complicated structure. Primary cilia play a critical role in craniofacial development, since defects in primary cilia are known to cause congenital craniofacial dysmorphologies as a wide spectrum of human diseases: the ciliopathies. The primary cilia also are known to regulate bone formation.

MicroRNAs control eyelid development through regulating Wnt signaling.

Background: The timing, location, and level of gene expression are crucial for normal organ development, because morphogenesis requires strict genetic control. MicroRNAs (miRNAs) are noncoding small single-stranded RNAs that play a critical role in regulating gene expression level. Although miRNAs are known to be involved in many biological events, the role of miRNAs in organogenesis is not fully understood.

Genes Show Spatiotemporal Expression during Murine Tongue and Eyelid Development.

The tongue is a critical organ, involved in functions such as speaking, swallowing, mastication, and degustation. Although genes are known to play critical roles in many biological processes, including organogenesis, the expression of the family members during tongue development remains unclear. We therefore performed a comparative hybridization analysis of 17 genes ( and ) during murine tongue development.

Lrp4/Wise regulates palatal rugae development through Turing-type reaction-diffusion mechanisms.

Periodic patterning of iterative structures is diverse across the animal kingdom. Clarifying the molecular mechanisms involved in the formation of these structure helps to elucidate the process of organogenesis. Turing-type reaction-diffusion mechanisms have been shown to play a critical role in regulating periodic patterning in organogenesis.

Expanding the Oro-Dental and Mutational Spectra of Kabuki Syndrome and Expression of and in Human Tooth Germs.

Kabuki syndrome is a rare genetic disorder characterized by distinct dysmorphic facial features, intellectual disability, and multiple developmental abnormalities. Despite more than 350 documented cases, the oro-dental spectrum associated with kabuki syndrome and expression of (histone-lysine N-methyltransferase 2D) or (lysine-specific demethylase 6A) genes in tooth development have not been well defined. Here, we report seven unrelated Thai patients with Kabuki syndrome having congenital absence of teeth, malocclusion, high-arched palate, micrognathia, and deviated tooth shape and size.

Regional regulation of Filiform tongue papillae development by Ikkα/Irf6.

Background: Non-gustatory filiform papillae play critical roles in helping to grip food, drawing food to the esophagus, cleaning the mouth, and spreading saliva. The molecular mechanisms of filiform tongue papillae development however are not fully understood.

Results: We found Ikkα and Irf6 expression in developing tongue epithelium, and describe here specific tongue abnormalities in mice with mutation of these genes, indicating a role for Ikkα and Irf6 in filiform papillae development.

Spatio-temporal expression of Sox genes in murine palatogenesis.

Members of the Sox gene family play critical roles in many biological processes including organogenesis. We carried out comparative in situ hybridisation analysis of seventeen Sox genes (Sox1-14, 17, 18 and 21) during murine palatogenesis from initiation to fusion of the palatal shelves above the dorsal side of the tongue. At palatal shelf initiation (E12.

Expression of Sox genes in tooth development.

Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium.

PKA regulatory subunit expression in tooth development.

Protein kinase A (PKA) plays critical roles in many biological processes including cell proliferation, cell differentiation, cellular metabolism and gene regulation. Mutation in PKA regulatory subunit, PRKAR1A has previously been identified in odontogenic myxomas, but it is unclear whether PKA is involved in tooth development. The aim of the present study was to assess the expression of alpha isoforms of PKA regulatory subunit (Prkar1a and Prkar2a) in mouse and human odontogenesis by in situ hybridization.

R-spondins/Lgrs expression in tooth development.

Background: Tooth development is highly regulated in mammals and it is regulated by networks of signaling pathways (e. g. Tnf, Wnt, Shh, Fgf and Bmp) whose activities are controlled by the balance between ligands, activators, inhibitors and receptors.

The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling.

Background: The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke's pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke's pouch.

Multiple postnatal craniofacial anomalies are characterized by conditional loss of polycystic kidney disease 2 (Pkd2).

Polycystin 2 (Pkd2), which belongs to the transient receptor potential family, plays a critical role in development. Pkd2 is mainly localized in the primary cilia, which also function as mechanoreceptors in many cells that influence multiple biological processes including Ca(2+) influx, chemical activity and signalling pathways. Mutations in many cilia proteins result in craniofacial abnormalities.

Cytoplasmic plaque formation in hemidesmosome development is dependent on SoxF transcription factor function.

Hemidesmosomes are composed of intricate networks of proteins, that are an essential attachment apparatus for the integrity of epithelial tissue. Disruption leads to blistering diseases such as epidermolysis bullosa. Members of the Sox gene family show dynamic and diverse expression patterns during development and mutation analyses in humans and mice provide evidence that they play a remarkable variety of roles in development and human disease.

Distinct roles of microRNAs in epithelium and mesenchyme during tooth development.

Background: Tooth development is known to be mediated by the cross-talk between signaling pathways, including Shh, Fgf, Bmp, and Wnt. MicroRNAs (miRNAs) are 19- to 25-nt noncoding small single-stranded RNAs that negatively regulate gene expression by binding target mRNAs, which is believed to be important for the fine-tuning signaling pathways in development. To investigate the role of miRNAs in tooth development, we examined mice with either mesenchymal (Wnt1Cre/Dicer(fl/fl)) or epithelial (ShhCre/Dicer(fl/fl)) conditional deletion of Dicer, which is essential for miRNA processing.

The role of Irf6 in tooth epithelial invagination.

Thickening and the subsequent invagination of the epithelium are an important initial step in ectodermal organ development. Ikkα has been shown to play a critical role in controlling epithelial growth, since Ikkα mutant mice show protrusions (evaginations) of incisor tooth, whisker and hair follicle epithelium rather than invagination. We show here that mutation of the Interferon regulatory factor (Irf) family, Irf6 also results in evagination of incisor epithelium.

Bmp signalling in filiform tongue papillae development.

Objective: Tongue papillae are critical organs in mastication. There are four different types of tongue papillae; fungiform, circumvallate, foliate, and filiform papillae. Unlike the other three taste papillae, non-gustatory papillae, filiform papillae cover the entire dorsal surface of the tongue and are important structures for the mechanical stress of sucking.