Mouth development

A mouth is present in all animals, and comprises an opening from the outside into the oral cavity and the beginnings of the digestive tract to allow eating. This review focuses on the earliest steps in mouth formation. In the first half, we conclude that the mouth arose once during evolution. In all animals, the mouth forms from ectoderm and endoderm. A direct association of oral ectoderm and digestive endoderm is present even in triploblastic animals, and in chordates, this region is known as the extreme anterior domain (EAD). Further support for a single origin of the mouth is a conserved set of genes that form a 'mouth gene program' including foxA and otx2. In the second half of this review, we discuss steps involved in vertebrate mouth formation, using the frog Xenopus as a model. The vertebrate mouth derives from oral ectoderm from the anterior neural ridge, pharyngeal endoderm and cranial neural crest (NC). Vertebrates form a mouth by breaking through the body covering in a precise sequence including specification of EAD ectoderm and endoderm as well as NC, formation of a 'pre-mouth array,' basement membrane dissolution, stomodeum formation, and buccopharyngeal membrane perforation. In Xenopus, the EAD is also a craniofacial organizer that guides NC, while reciprocally, the NC signals to the EAD to elicit its morphogenesis into a pre-mouth array. Human mouth anomalies are prevalent and are affected by genetic and environmental factors, with understanding guided in part by use of animal models. WIREs Dev Biol 2017, 6:e275. doi: 10.1002/wdev.275 For further resources related to this article, please visit the WIREs website

Impacts of Skeletal Anterior Open Bite Malocclusion on Speech

Introduction: Articulation problems are seen in 80% to 90% of dentofacial deformity (DFD) subjects compared with 5% of the general population, impacting communication and quality of life, but the causal link is unclear. We hypothesize there are both qualitative (perceptual) and quantitative (spectral) differences in properties of stop (/t/ or /k/), fricative (/s/ or /ʃ/), and affricate (/tʃ/) consonant sounds and that severity of anterior open bite (AOB) jaw disharmonies correlates with degree of speech abnormality. Methods: To test our hypotheses, surgical orthodontic records and audio recordings were collected from DFD patients (n = 39 AOB, 62 controls). A speech pathologist evaluated subjects, and recordings were analyzed using spectral moment analysis (SMA) to measure sound frequency distortions. Results: Perceptually, there is a higher prevalence of auditory and visual speech distortions in AOB DFD patients when compared to controls. Quantitatively, a significant (P < .01) increase in the centroid frequency (M1) was seen in the /k/, /t/, /tʃ/, and /s/ sounds of AOB subjects compared to the controls. Using linear regression, correlations between AOB skeletal severity and spectral distortion were found for /k/ and /t/ sounds. Conclusions: A higher prevalence of qualitative distortions and significant quantitative spectral distortions in consonant sounds were seen in AOB patients compared to controls. Additionally, severity of skeletal AOB is correlated with degree of distortion for consonant sounds. These findings provide insight into how the surgical and/or orthodontic treatment of AOB may impact speech

Molecular toxicity of lead

Thesis: S.B., Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences, 2008.Cataloged from PDF version of thesis.Includes bibliographical references (pages 23-28).Introduction - Lead is a heavy metal that has been in use for over 8000 years (White, 2007). It was first smelted it 4000BC as a byproduct of silver processing. Since then, Pb has played a dynamic role in history, possibly contributing to the fall of the Roman Empire (Nraigu, 1983). Pb is a highly malleable and ductile Group IVa metal. It has been utilized in a variety of products including makeup, water pipes, cooking vessels, wine bottle seals, glass, batteries, solder, electronic components, paint, and antiknock fuel additives (White, 2007). Its prevalent, long-term use has distributed anthropogenic Pb across the planet in soil, air-borne dust, and water (White, 2007). As a result, human exposure can occur via inhaled air, dust, food, and drinking water. Pb has no known biological functions, yet it has numerous detrimental effects on the body, several of which have been recognized for millennia.by Laura Jacox.S.B

Role of the Extreme Anterior Domain Organizer in Craniofacial Development

Craniofacial development is an intricate process, involving cranial neural crest (NC) and anterior facial tissue. NC migration is regulated by multiple mechanisms and activity of one or more organizer regions. Work presented here explores the role of the EAD, an organizer of craniofacial development in Xenopus, and its reciprocal signaling with cranial NC. The EAD later contributes to the mouth, nostrils, and anterior pituitary. EAD function involves the Kinin-Kallikrein pathway that was shown for the first time to be necessary for mouth formation. Facial transplants demonstrate that EAD-localized Kinin-Kallikrein function is required for migration of first arch cranial NC into the face. After migration, cranial NC signals back to the EAD to regulate mouth opening via the Wnt/PCP pathway. This pathway is associated with a process consistent with convergent extension of the EAD, whereby a wide and short epithelial mass narrows and lengthens, and cells and nuclei undergo stereotypical changes. The resultant EAD is a bilayered epithelium that later splits to form the mouth opening. Identification of the EAD as a NC organizer, reciprocal interaction of EAD and NC, and convergent extension associated with mouth formation has not previously been described during craniofacial development. Face formation is widely conserved, so findings in frog are likely relevant to amniotes and will provide insight into causes of craniofacial deformities.Biological Sciences in Dental Medicin

UNDERSTANDING TECHNOLOGY ADOPTION BY ORTHODONTISTS

Orthodontics is evolving due to advances in 3D imaging, printing, digital scanning and treatment planning. With digital tools, treatment may become more predictable, efficient and effective, while reducing side effects. Technologies are impacting patient care, but knowledge of adoption patterns is incomplete. We aim to identify adoption decision makers, information sources, incentives and barriers. Twenty-four privately practicing orthodontists were interviewed in a semi-structured format. Interview transcripts were analyzed to identify factors in technology adoption. Thematic patterns were established through iterative systematic analysis. After identifying adoption factors, we surveyed American Association of Orthodontics (AAO) members on their technology habits; data were assessed using descriptive and bivariate analyses. Survey responses reveal orthodontists make purchasing decisions independently of staff, after consulting other dentists and company representatives. Meetings and continuing education are influential information sources, while research literature is not. Early and middle adopters are integrating digital technologies into practice and view enhanced ease of use, capabilities, efficiency as primary incentives. Improving outcomes and patient comfort are not key motivators, whereas all interviewees view cost as the largest barrier. Orthodontists positively perceive the influence of technology, but are concerned that direct-to-consumer products will cause loss of market share. Understanding the technology adoption process can guide innovation to improve treatment and ease the transition into a digital workflow

Tissue-specific and ubiquitous expression patterns from alternative promoters of human genes.

Transcriptome diversity provides the key to cellular identity. One important contribution to expression diversity is the use of alternative promoters, which creates mRNA isoforms by expanding the choice of transcription initiation sites of a gene. The proximity of the basal promoter to the transcription initiation site enables prediction of a promoter's location based on the gene annotations. We show that annotation of alternative promoters regulating expression of transcripts with distinct first exons enables a novel methodology to quantify expression levels and tissue specificity of mRNA isoforms.The use of distinct alternative first exons in 3,296 genes was examined using exon-microarray data from 11 human tissues. Comparing two transcripts from each gene we found that the activity of alternative promoters (i.e., P1 and P2) was not correlated through tissue specificity or level of expression. Furthermore neither P1 nor P2 conferred any bias for tissue-specific or ubiquitous expression. Genes associated with specific diseases produced transcripts whose limited expression patterns were consistent with the tissue affected in disease. Notably, genes that were historically designated as tissue-specific or housekeeping had alternative isoforms that showed differential expression. Furthermore, only a small number of alternative promoters showed expression exclusive to a single tissue indicating that "tissue preference" provides a better description of promoter activity than tissue specificity. When compared to gene expression data in public databases, as few as 22% of the genes had detailed information for more than one isoform, whereas the remainder collapsed the expression patterns from individual transcripts into one profile.We describe a computational pipeline that uses microarray data to assess the level of expression and breadth of tissue profiles for transcripts with distinct first exons regulated by alternative promoters. We conclude that alternative promoters provide individualized regulation that is confirmed through expression levels, tissue preference and chromatin modifications. Although the selective use of alternative promoters often goes uncharacterized in gene expression analyses, transcripts produced in this manner make unique contributions to the cell that requires further exploration

Facial Transplants in Xenopus laevis Embryos

Craniofacial birth defects occur in 1 out of every 700 live births, but etiology is rarely known due to limited understanding of craniofacial development. To identify where signaling pathways and tissues act during patterning of the developing face, a 'face transplant' technique has been developed in embryos of the frog Xenopus laevis. A region of presumptive facial tissue (the "Extreme Anterior Domain" (EAD)) is removed from a donor embryo at tailbud stage, and transplanted to a host embryo of the same stage, from which the equivalent region has been removed. This can be used to generate a chimeric face where the host or donor tissue has a loss or gain of function in a gene, and/or includes a lineage label. After healing, the outcome of development is monitored, and indicates roles of the signaling pathway within the donor or surrounding host tissues. Xenopus is a valuable model for face development, as the facial region is large and readily accessible for micromanipulation. Many embryos can be assayed, over a short time period since development occurs rapidly. Findings in the frog are relevant to human development, since craniofacial processes appear conserved between Xenopus and mammals.National Institutes of Health (U.S.) (Grant R01DE021109)Harvard University (Herschel Smith Graduate Fellowship)National Institute of Dental and Craniofacial Research (U.S.) (Fellowship Grant F30DE022989-01