Math1: an essential gene for the generation of inner ear hair cells.

The mammalian inner ear contains the cochlea and vestibular organs, which are responsible for hearing and balance, respectively. The epithelia of these sensory organs contain hair cells that function as mechanoreceptors to transduce sound and head motion. The molecular mechanisms underlying hair cell development and differentiation are poorly understood. Math1, a mouse homolog of the Drosophila proneural gene atonal, is expressed in inner ear sensory epithelia. Embryonic Math1-null mice failed to generate cochlear and vestibular hair cells. This gene is thus required for the genesis of hair cells.

atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain.

Drosophila atonal (ato) is the proneural gene of the chordotonal organs (CHOs) in the peripheral nervous system (PNS) and the larval and adult photoreceptor organs. Here, we show that ato is expressed at multiple stages during the development of a lineage of central brain neurons that innervate the optic lobes and are required for eclosion. A novel fate mapping approach shows that ato is expressed in the embryonic precursors of these neurons and that its expression is reactivated in third instar larvae (L3). In contrast to its function in the PNS, ato does not act as a proneural gene in the embryonic brain. Instead, ato performs a novel function, regulating arborization during larval and pupal development by interacting with Notch.

Proprioceptor pathway development is dependent on Math1.

The proprioceptive system provides continuous positional information on the limbs and body to the thalamus, cortex, pontine nucleus, and cerebellum. We showed previously that the basic helix-loop-helix transcription factor Math1 is essential for the development of certain components of the proprioceptive pathway, including inner-ear hair cells, cerebellar granule neurons, and the pontine nuclei. Here, we demonstrate that Math1 null embryos lack the D1 interneurons and that these interneurons give rise to a subset of proprioceptor interneurons and the spinocerebellar and cuneocerebellar tracts. We also identify three downstream genes of Math1 (Lh2A, Lh2B, and Barhl1) and establish that Math1 governs the development of multiple components of the proprioceptive pathway.

skittles, a Drosophila phosphatidylinositol 4-phosphate 5-kinase, is required for cell viability, germline development and bristle morphology, but not for neurotransmitter release.

The phosphatidylinositol pathway is implicated in the regulation of numerous cellular functions and responses to extracellular signals. An important branching point in the pathway is the phosphorylation of phosphatidylinositol 4-phosphate by the phosphatidylinositol 4-phosphate 5-kinase (PIP5K) to generate the second messenger phosphatidylinositol 4,5-bis-phosphate (PIP2). PIP5K and PIP2 have been implicated in signal transduction, cytoskeletal regulation, DNA synthesis, and vesicular trafficking. We have cloned and generated mutations in a Drosophila PIP5K type I (skittles). Our analysis indicates that skittles is required for cell viability, germline development, and the proper structural development of sensory bristles. Surprisingly, we found no evidence for PIP5KI involvement in neural secretion.

Influence of scan setting selections on root canal visibility with cone beam CT.

OBJECTIVES: The aim of this study was to assess the influence of scan setting selection, including field of view (FOV) ranging from small to large, number of projections and scan modes on the visibility of the root canal with cone beam CT (CBCT). METHODS: One human mandible cadaver was scanned with CBCT (Accuitomo 170; J Morita MPG Corp., Kyoto, Japan) using six different FOVs (4×4 cm, 6×6 cm, 8×8 cm, 10×10 cm, 14×10 cm and 17×12 cm) with either 360 or 180 projections in standard and high resolution. The right canine was selected for evaluation. Ten observers independently assessed the visibility of the canal space and overall image quality on a five-point scale. RESULTS: The results indicate that both selections of FOV and number of projections have significant influence on root canal visibility (p=0.0001), whereas scan mode, whether standard or high resolution, was less relevant (p=0.34). CONCLUSIONS: The smallest FOV available should always be used for endodontic applications, and it is not recommended to reduce the number of projections to 180. Using the standard scan mode instead of high resolution does not negatively influence the visibility of the root canal space and is therefore recommended.

Evaluation of web-based instruction for anatomical interpretation in maxillofacial cone beam computed tomography.

OBJECTIVES: To evaluate the effectiveness of a web-based instruction in the interpretation of anatomy in images acquired with maxillofacial cone beam CT (CBCT). METHODS: An interactive web-based education course for the interpretation of craniofacial CBCT images was recently developed at our institution. Self-evaluation modules on correlative anatomical features were also included to support the learning process. Three e-learner groups were selected to evaluate the effectiveness of the educational modules. The three groups were (1) oral health specialists (OHSs) (comprising periodontologists, prosthodontists, orthodontists and maxillofacial surgeons); (2) third grade (DS3) and (3) first grade (DS1) undergraduate dental students. The assessment modules that were part of the interactive web-course content were administered after delivery of the course material. In addition, each group received a computer affinity questionnaire to quantify the extent of knowledge about computers and a perception questionnaire to assess their attitudes toward the web-course. RESULTS: The OHS group yielded significantly better scoring results in the post-course test than the pre-course test. However, no statistically significant differences in test scores were found for both undergraduate student groups (DS1 and DS3). All groups presented a highly positive attitude towards the web-course, as was demonstrated by the post-course perception questionnaire. CONCLUSIONS: The present CBCT educational course is an effective didactic method for teaching OHSs the anatomical interpretation of CBCT multiplanar reformatted images and, for undergraduate students, it was found to be as effective as conventional educational methods in dentistry. The efficacy of a web-based educational course requires further evaluation.

A web-based instruction module for interpretation of craniofacial cone beam CT anatomy.

OBJECTIVES: To develop a web-based module for learner instruction in the interpretation and recognition of osseous anatomy on craniofacial cone-beam CT (CBCT) images. METHODS: Volumetric datasets from three CBCT systems were acquired (i-CAT, NewTom 3G and AccuiTomo FPD) for various subjects using equipment-specific scanning protocols. The datasets were processed using multiple software to provide two-dimensional (2D) multiplanar reformatted (MPR) images (e.g. sagittal, coronal and axial) and three-dimensional (3D) visual representations (e.g. maximum intensity projection, minimum intensity projection, ray sum, surface and volume rendering). Distinct didactic modules which illustrate the principles of CBCT systems, guided navigation of the volumetric dataset, and anatomic correlation of 3D models and 2D MPR graphics were developed using a hybrid combination of web authoring and image analysis techniques. Interactive web multimedia instruction was facilitated by the use of dynamic highlighting and labelling, and rendered video illustrations, supplemented with didactic textual material. HTML coding and Java scripting were heavily implemented for the blending of the educational modules. RESULTS: An interactive, multimedia educational tool for visualizing the morphology and interrelationships of osseous craniofacial anatomy, as depicted on CBCT MPR and 3D images, was designed and implemented. CONCLUSIONS: The present design of a web-based instruction module may assist radiologists and clinicians in learning how to recognize and interpret the craniofacial anatomy of CBCT based images more efficiently.

From skin to nerve: flies, vertebrates and the first helix.

Vertebrate and invertebrate nervous tissue is derived from early embryonic ectoderm, which also gives rise to epidermal derivatives such as skin. Proneural basic helix-loop-helix (bHLH) transcription factors are the key players in the formation of peripheral nervous system (PNS) and central nervous system (CNS) from naïve ectoderm to differentiated postmitotic neurons. The comparative approach and the use of a wide range of animal models have led to increasingly comprehensive investigations of this issue in the last decade. This review will focus on current studies of neural development in vertebrate and invertebrate PNS and on understanding how the bHLH domain structure encodes multiple functions required for neural specification.

Functional conservation of atonal and Math1 in the CNS and PNS.

To determine the extent to which atonal and its mouse homolog Math1 exhibit functional conservation, we inserted (beta)-galactosidase (lacZ) into the Math1 locus and analyzed its expression, evaluated consequences of loss of Math1 function, and expressed Math1 in atonal mutant flies. lacZ under the control of Math1 regulatory elements duplicated the previously known expression pattern of Math1 in the CNS (i.e., the neural tube, dorsal spinal cord, brainstem, and cerebellar external granule neurons) but also revealed new sites of expression: PNS mechanoreceptors (inner ear hair cells and Merkel cells) and articular chondrocytes. Expressing Math1 induced ectopic chordotonal organs (CHOs) in wild-type flies and partially rescued CHO loss in atonal mutant embryos. These data demonstrate that both the mouse and fly homologs encode lineage identity information and, more interestingly, that some of the cells dependent on this information serve similar mechanoreceptor functions.