Sonographic measurement of ear length among normal fetuses of pregnant Igbo women in port Harcourt, Nigeria.

BACKGROUND: Fetal ear length measurement has been associated with some clinical values: sonographic marker for chromosomal aneuploidy and for biometric estimation of fetal gestational age. OBJECTIVES: To establish a baseline reference value for fetal ear length and to assess relationship between fetal ear length and gestational age. METHODS: Ear length measurements were obtained prospectively from fetuses in 551 normal singleton pregnancies of 15 to 41 weeks gestation. Normal cases were defined as normal sonographic findings during examination plus normal infant post-delivery. The relationship between gestational age (GA) in weeks and fetal ear length (FEL) in millimeters were analyzed by simple linear regression. Correlation of FEL measurements with GA, biparietal diameter (BPD), Head circumference (HC), Abdominal Circumference (AC), Femur Length (FL) and maternal age (MA) were also obtained. RESULTS: Linear relationships were found between FEL and GA (FEL=0.872GA-2.972). There was a high correlation between FEL and GA (r = 0.837; P = .001). Good linear relationship and strong positive correlation were demonstrated between FEL and BPD, AC, HC, and FL (p<0.05). CONCLUSION: The result of this study provides normal baseline reference value for FEL. The study also showed good linear relationship and good correlation between FEL and fetal biometric measurements.

The Many Faces of Persistent Stapedial Artery: CT Findings and Embryologic Explanations.

Persistent stapedial artery is a vascular anomaly with both clinical and surgical implications. Because of its scarcity, however, it remains underrecognized on imaging. Presented here is a series of 10 cases, demonstrating characteristic CT findings associated with this vascular anomaly and its most common pathognomonic imaging signs. The variable morphologic configurations and their corresponding embryologic underpinnings are described. Clinical and surgical implications of this rare anomaly are discussed.

Ear asymmetry in Tengmalm's owl (Aegolius funereus): Two phases of asymmetrical development of the squamoso-occipital wing.

Ear asymmetry is an adaptive characteristic present in the order of owls (Strigiformes). It developed independently up to seven times in this taxon and is accompanied by morphological adaptations in bones or soft tissues around or at the ear openings. Within all strigiform species, the Boreal or Tengmalm's owl (Aegolius funereus) possesses a particularly complex bilateral ear asymmetry that results from modifications of the neurocranium and some cartilaginous elements. While the ear asymmetry in adult birds has been described in detail, data on its development is scarce. Here we describe the development of the asymmetric squamoso-occipital wing of A. funereus from its embryonic origin up to adulthood. The asymmetry of the squamoso-occipital wing develops in two phases. Firstly, it originates as a cartilaginous structure in the last ten days before hatching. Its frontal margin shows a bilateral asymmetry from the beginning of its development while the rostro-ventral process stays symmetrical up to post-hatching day 35. Secondly, when the fledglings have already left the nest, the squamoso-occipital wing ossifies. Moreover, the rostro-ventral process on the right side grows towards the eyeball, while there is no relative displacement on the left side. Thus, the developmental process in A. funereus differs from that in the barn owl that develops its soft tissue asymmetry in one phase and completes the asymmetry before hatching. The new data presented here extend our knowledge of the mechanisms underlying the asymmetric skull development in owls.

Histological development and integration of the Zebrafish Weberian apparatus.

BACKGROUND: The Weberian apparatus enhances hearing in otophysan fishes, including Zebrafish (Danio rerio). Several studies have examined aspects of morphological development of the Weberian apparatus and hearing ability in Zebrafish. A comprehensive developmental description including both hard and soft tissues is lacking. This information is critical for both interpretation of genetic developmental analyses and to better understand the role of morphogenesis and integration on changes in hearing ability. RESULTS: Histological development of hard and soft tissues of the Weberian apparatus, including ossicles, ear, swim bladder, and ligaments are described from early larval stages (3.8 mm notochord length) through adult. Results show a strong relationship in developmental timing and maturation across all regions. All required auditory elements are present and morphologically integrated early, by 6.5 mm SL. Dynamic ossification patterns and changes in shape continue throughout the examined developmental period. CONCLUSIONS: This study provides the first comprehensive histological description of Weberian apparatus development in Zebrafish. Morphological integration was found early, before increases in hearing ability were detected in functional studies (>10 mm total length), suggesting morphological integration precedes functional integration. Further research is needed to examine the nature of the functional delay, and how maturation of the Weberian apparatus influences functionality.

Enhancer activation by FGF signalling during otic induction.

Vertebrate ear progenitors are induced by fibroblast growth factor signalling, however the molecular mechanisms leading to the coordinate activation of downstream targets are yet to be discovered. The ear, like other sensory placodes, arises from the pre-placodal region at the border of the neural plate. Using a multiplex NanoString approach, we determined the response of these progenitors to FGF signalling by examining the changes of more than 200 transcripts that define the otic and other placodes, neural crest and neural plate territories. This analysis identifies new direct and indirect FGF targets during otic induction. Investigating changes in histone marks by ChIP-seq reveals that FGF exposure of pre-placodal cells leads to rapid deposition of active chromatin marks H3K27ac near FGF-response genes, while H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elements controlling otic gene expression in time and space and define a unique transcription factor signature likely to control their activity. Finally, we show that in response to FGF signalling the transcription factor dimer AP1 recruits the histone acetyl transferase p300 to selected otic enhancers. Thus, during ear induction FGF signalling modifies the chromatin landscape to promote enhancer activation and chromatin accessibility.

Phenotypic analysis of mice carrying human-type MAFB p.Leu239Pro mutation.

The transcription factor, MafB, plays important role in the differentiation and functional maintenance of various cells and tissues, such as the inner ear, kidney podocyte, parathyroid gland, pancreatic islet, and macrophages. The rare heterozygous substitution (p.Leu239Pro) of the DNA binding domain in MAFB is the cause of Focal Segmental Glomerulosclerosis associated with Duane Retraction Syndrome, which is characterized by impaired horizontal eye movement due to cranial nerve maldevelopment in humans. In this research, we generated mice carrying MafB p.Leu239Pro (Mafbmt/mt) and retrieved their tissues for analysis. As a result, we found that the phenotype of Mafbmt/mt mouse was similar to that of the conventional Mafb deficient mouse. This finding suggests that the Leucine residue at 239 in the DNA binding domain plays a key role in MafB function and could contribute to the diagnosis or development of treatment for patients carrying the MafB p.Leu239Pro missense variant.

Anteroposterior patterning of the zebrafish ear through Fgf- and Hh-dependent regulation of hmx3a expression.

In the zebrafish, Fgf and Hh signalling assign anterior and posterior identity, respectively, to the poles of the developing ear. Mis-expression of fgf3 or inhibition of Hh signalling results in double-anterior ears, including ectopic expression of hmx3a. To understand how this double-anterior pattern is established, we characterised transcriptional responses in Fgf gain-of-signalling or Hh loss-of-signalling backgrounds. Mis-expression of fgf3 resulted in rapid expansion of anterior otic markers, refining over time to give the duplicated pattern. Response to Hh inhibition was very different: initial anteroposterior asymmetry was retained, with de novo duplicate expression domains appearing later. We show that Hmx3a is required for normal anterior otic patterning, and that otic patterning defects in hmx3a-/- mutants are a close phenocopy to those seen in fgf3-/- mutants. However, neither loss nor gain of hmx3a function was sufficient to generate full ear duplications. Using our data to infer a transcriptional regulatory network required for acquisition of otic anterior identity, we can recapitulate both the wild-type and the double-anterior pattern in a mathematical model.

The location of the fetal ears: A hint for prenatal diagnosis of agnathia-otocephaly complex.

Otocephaly is an extremely rare lethal congenital anomaly characterized by the absence or underdevelopment of the mandible. The clinical presentation is variable. Some cases may present with severe micrognathia as the only anomaly seen prenatally. The key to early diagnosis is careful assessment of the location of the fetal ears on 2D ultrasound examination.

Prenatal development of the sound transmitting apparatus in different embryonic stages of Malpolon monsspesulanus (squamata-serpentes) / Desenvolvimento pré-natal do aparelho transmissor de som em diferentes estágios embrionários de Malpolon monsspesulanus (Squamata-serpentes)

Abstract The developmental investigation of sound transmitting apparatus is important in understanding the ontogenetic processes behind morphological diversity. The development of sound conducting apparatus was studied in Montpellier snake; Malpolon monspessulanus at 6.5, 7.2, 8.3 and 9.3 cm total body lengths using light microscopy study. The columella auris firstly appeared as undifferentiated rod shape mesenchymal cells. As the growth proceeded, it chondrified and differentiates into two main parts. In addition, the viscerocranium components which participate in formation of sound transmitting apparatus undergo critical organization. In more advanced stages, procartilagenous stylohyal chondrified and fuse with the well organized quadrate. These data considered as a base for functional and molecular mechanisms of sound transmitting apparatus studies and identification of diseases that may infect them.

Resumo A investigação do desenvolvimento de equipamentos de transmissão de som é importante na compreensão dos processos ontogenéticos atrás diversidade morfológica. O desenvolvimento de aparelhos de som realização foi estudada em Montpellier cobra; Monspessulanus Malpolon em 6.5, 7.2, 8.3 e 9.3 cm corporal total utilizando comprimentos de estudo de microscopia de luz. O auris columelar em primeiro lugar apareceu como células mesenquimais forma haste indiferenciada. Como o crescimento passou, ele chondrified e diferencia em duas partes principais. Além disso, os componentes viscerocrânio que participam na formação do aparelho de transmissão de som submeter a organização crítico. Em estágios mais avançados, stylohyal procartilagenous chondrified e se fundem com o quadrado bem organizado. Estes dados considerados como uma base para os mecanismos funcionais e estudos moleculares do aparelho de transmissão de som e identificação de doenças que podem infectar-los.

Prenatal development of the sound transmitting apparatus in different embryonic stages of Malpolon monsspesulanus (squamata-serpentes).

The developmental investigation of sound transmitting apparatus is important in understanding the ontogenetic processes behind morphological diversity. The development of sound conducting apparatus was studied in Montpellier snake; Malpolon monspessulanus at 6.5, 7.2, 8.3 and 9.3 cm total body lengths using light microscopy study. The columella auris firstly appeared as undifferentiated rod shape mesenchymal cells. As the growth proceeded, it chondrified and differentiates into two main parts. In addition, the viscerocranium components which participate in formation of sound transmitting apparatus undergo critical organization. In more advanced stages, procartilagenous stylohyal chondrified and fuse with the well organized quadrate. These data considered as a base for functional and molecular mechanisms of sound transmitting apparatus studies and identification of diseases that may infect them.

Prenatal and postnatal development of the mammalian ear.

The ear can be subdivided into three distinct parts, each with significantly distinct structural and functional differences, the outer, middle, and inner ear, the latter housing the specialized sensory hair cells that act as transducers. There are numerous manuscripts documenting the anatomical development of the inner, middle, and outer ear in humans, rodents, chick, and zebrafish, dating back to the early 20th Century, and these developmental processes of these components are further compared in a number of review articles (Anthwal & Thompson, ; Basch, Brown, Jen, & Groves, ; Sai & Ladher, ). This article presents a review of both pre- and postnatal development of the inner ear, discusses recent molecular genetic advances toward our understanding of hair cells responsible for the sensory functions of the inner ear. Finally, a survey of comparative ear biology is used to pull together our understanding of the species differences, similarities, and key time points of definitive organ development of the ear.

Development of ear asymmetry in the American barn owl (Tyto furcata pratincola).

Owls are known for their nocturnal hunting capability. Many owl species are able to localize prey in complete darkness just by hearing. Sound localization of strictly nocturnal owls is improved by asymmetrically arranged outer ears. According to Norberg (1977), who worked with adult owls, asymmetrical ears evolved at least four times independently among owls. What is unknown so far is how the ear asymmetry develops in the embryo. Here we examine the embryonic development of ear asymmetry in the American barn owl (Tyto furcata pratincola) in the frame of the 42 stages suggested by Köppl et al. (2005). In this species, the left ear opening in the skin is located higher than its counterpart on the right. Micro-CT scans show that in an anatomically defined coordinate system, the ear openings initially appear symmetrically as does the skull as well as the eyes, the nasal openings, the stapes and the squamosum. The ear openings are initially located ventrally in the skull. Soon after their appearance, the ear openings start to move dorso-occipitally. At the developmental stages 36-39, the left ear opening moves faster than the right one. In this way, an ear asymmetry develops within a few developmental stages. The skull and the other anatomical markers remain symmetrical. Thus, these data show that the soft tissue asymmetry in the barn owl develops already before hatching. It will be interesting to compare the time course described here with the time course of development in owl species with bony ear asymmetries.

Pioneer neurog1 expressing cells ingress into the otic epithelium and instruct neuronal specification.

Neural patterning involves regionalised cell specification. Recent studies indicate that cell dynamics play instrumental roles in neural pattern refinement and progression, but the impact of cell behaviour and morphogenesis on neural specification is not understood. Here we combine 4D analysis of cell behaviours with dynamic quantification of proneural expression to uncover the construction of the zebrafish otic neurogenic domain. We identify pioneer cells expressing neurog1 outside the otic epithelium that migrate and ingress into the epithelialising placode to become the first otic neuronal progenitors. Subsequently, neighbouring cells express neurog1 inside the placode, and apical symmetric divisions amplify the specified pool. Interestingly, pioneer cells delaminate shortly after ingression. Ablation experiments reveal that pioneer cells promote neurog1 expression in other otic cells. Finally, ingression relies on the epithelialisation timing controlled by FGF activity. We propose a novel view for otic neurogenesis integrating cell dynamics whereby ingression of pioneer cells instructs neuronal specification.

Role of skeletal muscle in ear development.

The current paper is a continuation of our work described in Rot and Kablar, 2010. Here, we show lists of 10 up- and 87 down-regulated genes obtained by a cDNA microarray analysis that compared developing Myf5-/-:Myod-/- (and Mrf4-/-) petrous part of the temporal bone, containing middle and inner ear, to the control, at embryonic day 18.5. Myf5-/-:Myod-/- fetuses entirely lack skeletal myoblasts and muscles. They are unable to move their head, which interferes with the perception of angular acceleration. Previously, we showed that the inner ear areas most affected in Myf5-/-:Myod-/- fetuses were the vestibular cristae ampullaris, sensitive to angular acceleration. Our finding that the type I hair cells were absent in the mutants' cristae was further used here to identify a profile of genes specific to the lacking cell type. Microarrays followed by a detailed consultation of web-accessible mouse databases allowed us to identify 6 candidate genes with a possible role in the development of the inner ear sensory organs: Actc1, Pgam2, Ldb3, Eno3, Hspb7 and Smpx. Additionally, we searched for human homologues of the candidate genes since a number of syndromes in humans have associated inner ear abnormalities. Mutations in one of our candidate genes, Smpx, have been reported as the cause of X-linked deafness in humans. Our current study suggests an epigenetic role that mechanical, and potentially other, stimuli originating from muscle, play in organogenesis, and offers an approach to finding novel genes responsible for altered inner ear phenotypes.

3D Ultrasound Evaluation of the Fetal Ear - Comparison of an xMatrix Probe with a Conventional Mechanical Probe.

Purpose New 3 D technologies like xMatrix probes promise superiority over conventional mechanical probes and may allow a more detailed and time-saving prenatal diagnosis. In a comparison study we evaluate fetal ears. The aim of our study was to compare the following aspects of both techniques: (1) ultrasound detail resolution, (2) raw data acquisition time (AT) and (3) influence of covariates. Materials and Methods 3 D raw data volumes of the fetal ear were collected with the V6 - 2 (V6) and with the xMatrix (X6) probe and were stored after offline customization to a single picture. Two observers scored these images independently. Furthermore, the 3 D raw data acquisition time (AT) was recorded. Concordance between observers, maternal age, body mass index (BMI), weeks of gestation and location of the placenta were evaluated. Results Data volumes of 103 patients were analyzed. The X6 detected anatomic structures like the scapha (p = 0.0146), fossa triangularis (p = 0.0075) and cymba conchae (p = 0.0025) more often. The mean AT of the X6 was shorter compared to the V6 (p < 0.0001). A placenta location in the scanning field increased the AT only for the V6 (p < 0.01). Concordance between observers was higher for the X6 in most cases. Detailed structures were less visible at the end of pregnancy for both devices. Conclusion The comparison study demonstrated clear advantages of the new xMatrix technology concerning an advanced and fast examination of detailed structures like the fetal ear. The importance of 3 D assessment in cases of fetal ear anomaly should be proven in further studies.

Lectins selectively label cartilage condensations and the otic neuroepithelium within the embryonic chicken head.

Cartilage morphogenesis during endochondral ossification follows a progression of conserved developmental events. Cells are specified towards a prechondrogenic fate and subsequently undergo condensation followed by overt differentiation. Currently available molecular markers of prechondrogenic and condensing mesenchyme rely on common regulators of the chondrogenic program that are not specific to the tissue type or location. Therefore tissue-specific condensations cannot be distinguished based on known molecular markers. Here, using the chick embryo model, we utilized lectin labeling on serial sections, demonstrating that differential labeling by peanut agglutinin (PNA) and Sambucus nigra agglutinin (SNA) successfully separates adjacently located condensations in the proximal second pharyngeal arch. PNA selectively labels chick middle ear columella and basal plate condensation, whereas SNA specifically marks extracolumella and the ventro-lateral part of the otic capsule. We further extended our study to examine lectin-binding properties of the different parts of the inner ear epithelium, neural tube and notochord. Our results show that SNA labels the auditory and vestibular hair cells of the inner ear, whereas PNA specifically recognizes the statoacoustic ganglion. PNA is also highly specific for the floor plate of the neural tube. Additionally, wheat germ agglutinin (WGA) labels the basement membrane of the notochord and is a marker of the apical-basal polarity of the cochlear duct. Overall, this study indicates that selective lectin labeling is a promising approach to differentiate between contiguously located mesenchymal condensations and subregions of epithelia globally during development.

Fraser syndrome: features suggestive of prenatal diagnosis in a review of 38 cases.

OBJECTIVE: Fraser syndrome (FS) is a rare malformation recessive disorder. Major criteria are cryptophtalmos, syndactyly, respiratory, genital and urinary tract anomalies. Few prenatal presentations have been reported. METHOD: We analyzed the prenatal and postnatal fetal phenotype in 38 cases of FS, including 25 pregnancy termination cases, 8 intra-uterine death cases and 4 cases that died after birth. RESULTS: Including both prenatal and postnatal fetal phenotypic evaluation, all cases presented dysmorphic features with nose and ear dysplasia. Renal anomalies and syndactyly were present in 37/38 cases, cryptophtalmos in 36/38, airways anomalies in 30/37 and genital anomalies in 30/35 cases. Anomalies of the abdominal wall such as low set umbilicus and omphalocele were found in 31 cases. Among the 26 cases for which ultrasound data were available, detectable anomalies included oligohydramnios (22), ascites/hydrops (9), renal anomalies (20), evidence for high airways obstruction (11), ophthalmologic anomalies (4), ear dysplasia (2) and syndactyly (2). CONCLUSION: This study shows that the postnatal phenotype of FS is very specific, whereas oligohydramnios hampers the prenatal recognition of the cardinal FS diagnosis criteria. Association of oligohydramnios, kidney agenesis and CHAOS should lead to consider this diagnosis. © 2016 John Wiley & Sons, Ltd.