Assessing Bayesian Phylogenetic Information Content of Morphological Data Using Knowledge from Anatomy Ontologies

Morphology remains a primary source of phylogenetic information for many groups of organisms, and the only one for most fossil taxa. Organismal anatomy is not a collection of randomly assembled and independent "parts", but instead a set of dependent and hierarchically nested entities resulting from ontogeny and phylogeny. How do we make sense of these dependent and at times redundant characters? One promising approach is using ontologies---structured controlled vocabularies that summarize knowledge about different properties of anatomical entities, including developmental and structural dependencies. Here we assess whether the proximity of ontology-annotated characters within an ontology predicts evolutionary patterns. To do so, we measure phylogenetic information across characters and evaluate if it is hierarchically structured by ontological knowledge---in much the same way as phylogeny structures across-species diversity. We implement an approach to evaluate the Bayesian phylogenetic information (BPI) content and phylogenetic dissonance among ontology-annotated anatomical data subsets. We applied this to datasets representing two disparate animal groups: bees (Hexapoda: Hymenoptera: Apoidea, 209 chars) and characiform fishes (Actinopterygii: Ostariophysi: Characiformes, 463 chars). For bees, we find that BPI is not substantially structured by anatomy since dissonance is often high among morphologically related anatomical entities. For fishes, we find substantial information for two clusters of anatomical entities instantiating concepts from the jaws and branchial arch bones, but among-subset information decreases and dissonance increases substantially moving to higher-level subsets in the ontology. We further applied our approach to addressing particular evolutionary hypotheses with an example of morphological evolution in miniature fishes. While we show that ontology does indeed structure phylogenetic information, additional relationships and processes, such as convergence, likely play a substantial role in explaining BPI and dissonance, and merit future investigation. Our work demonstrates how complex morphological datasets can be interrogated with ontologies by allowing one to access how information is spread hierarchically across anatomical concepts, how congruent this information is, and what sorts of processes may structure it: phylogeny, development, or convergence.

Branchial Sinus with Cyst - Two Case Reports with Review of Literature

Branchial cleft anomalies are well described, with the second arch anomaly being the commonest. Remains of cervical sinus of His may persist as a branchial cyst. A branchial sinus is formed when 2nd branchial arch fails to meet the 5th pharyngeal arch. Peak age for presentation of branchial cysts is in the third decade and that of the congenital sinuses and fistulae is at birth. The association of a branchial cyst with branchial sinus is very rare. We are presenting two cases had branchial cyst along with branchial sinus. It was managed successfully with complete excision. Histopathological examination confirmed the association. Keywords: Branchial Sinus, Branchial cyst,

The effects of altered BMP4 signaling in first branchial-arch-derived murine embryonic orofacial tissues

The first branchial arch (BA1), which is derived from cranial neural crest (CNC) cells, gives rise to various orofacial tissues. Cre mice are widely used for the determination of CNC and exploration of gene functions in orofacial development. However, there is a lack of Cre mice specifically marked BA1’s cells. Pax2-Cre allele was previously generated and has been widely used in the field of inner ear development. Here, by compounding Pax2-Cre and R26R-mTmG mice, we found a specific expression pattern of Pax2+ cells that marked BA1’s mesenchymal cells and the BA1-derivatives. Compared to Pax2-Cre; R26R-mTmG allele, GFP+ cells were abundantly found both in BA1 and second branchial arch in Wnt1-Cre;R26R-mTmG mice. As BMP4 signaling is required for orofacial development, we over-activated Bmp4 by using Pax2-Cre; pMes-BMP4 strain. Interestingly, our results showed bilateral hyperplasia between the upper and lower teeth. We also compare the phenotypes of Wnt1-Cre; pMes-BMP4 and Pax2-Cre; pMes-BMP4 strains and found severe deformation of molar buds, palate, and maxilla-mandibular bony structures in Wnt1-Cre; pMes-BMP4 mice; however, the morphology of these orofacial organs were comparable between controls and Pax2-Cre; pMes-BMP4 mice except for bilateral hyperplastic tissues. We further explore the properties of the hyperplastic tissue and found it is not derived from Runx2+ cells but expresses Msx1, and probably caused by abnormal cell proliferation and altered expression pattern of p-Smad1/5/8. In sum, our findings suggest altering BMP4 signaling in BA1-specific cell lineage may lead to unique phenotypes in orofacial regions, further hinting that Pax2-Cre mice could be a new model for genetic manipulation of BA1-derived organogenesis in the orofacial region.

A rare case of co-existing branchial cyst and thyroglossal cyst

<p class="abstract">Thyroglossal duct remnants and branchial arch anomalies are the most common congenital neck masses. These anomalies typically present in childhood or early adulthood as cysts, sinuses or cartilaginous remnants, but may rarely present in late adulthood. Although both thyroglossal duct remnants and branchial cysts may be encountered individually, these anomalies are rarely encountered together in the same individual. We report the third such case of co-existing branchial cyst and thyroglossal cyst occurring in the same individual with review of embryological development of thyroglossal duct cysts and second branchial arch anomalies.</p>

AN INSIGHT INTO - HEMIFACIAL MICROSOMIA

Hemifacial microsomia is a common birth defect involving first and second branchial arch derivatives. The phenotype is highly variable. In addition to craniofacial anomalies, there may be cardiac, vertebral, and central nervous system defects. Most cases are sporadic, but there are rare familial cases that exhibit autosomal dominant inheritance.

First branchial arch cyst in an elderly patient: diagnostic dilemma and subsequent management

The branchial system plays a significant role in the embryological development of the many internal and external human body structures. Failure of normal development of these systems may result in branchial system anomalies. Anomalies of the first branchial cleft are rare and account for 1–8% of all branchial anomalies. They have an incidence of 1 per 1 million births, most of which are diagnosed in early childhood. We present an unusual case of a first branchial arch cyst in an elderly gentleman: a 65-year-old man who presented with a persistent swelling in the left pre-auricular region with no associated sinus, fistulae or lymphadenopathy and with an intact facial nerve. Investigations including fine needle aspiration, ultrasound and magnetic resonance imaging led to the diagnosis of a lesion of salivary origin and an extracapsular dissection was undertaken. The histological appearance on excision was, however, in keeping with a first arch branchial cyst. In conclusion, the nonspecific clinical and radiological presentation of first branchial arch anomalies may lead to difficulty and often delay in the diagnosis of these lesions, particularly in elderly patients as it is more often associated with childhood and adolescence. A high level of suspicion is mandatory to prevent inappropriate management in the form of incision and drainage, which further increases the risk of recurrence and facial nerve injury at the time of formal excision due to scarring.

Generation of a new six1-null line in Xenopus tropicalis for study of development and congenital disease

The vertebrate Six (Sine oculis homeobox) family of homeodomain transcription factors play critical roles in the development of several organs. Six1 plays a central role in cranial placode development, including the precursor tissues of the inner ear, as well as other cranial sensory organs and the kidney. In humans, mutations in SIX1 underlie some cases of branchio-oto-renal syndrome (BOR), which is characterized by moderate to severe hearing loss. We utilized CRISPR/Cas9 technology to establish a six1 mutant line in Xenopus tropicalis that is available to the research community. We demonstrate that at larval stages, the six1-null animals show severe disruptions in gene expression of putative Six1 target genes in the otic vesicle, cranial ganglia, branchial arch and neural tube. At tadpole stages, six1-null animals display dysmorphic Meckel's, ceratohyal and otic capsule cartilage morphology. This mutant line will be of value for the study of the development of several organs as well as congenital syndromes that involve these tissues.

BRANCHIO-OTO-RENAL (BOR) SYNDROME

Introduction. This work is devoted to the problem of embryology of the ears and kidneys. First ear and kidney abnormalities were reported in 1946 by Edith Potter’s association of crumpled and flattened ears with bilateral kidney agenesis. Ear malformations are associated with an increased frequency of clinically significant structural renal anomalies compared with the general population. These include specific multiple congenital anomaly syndromes, Townes-Brocks syndrome, branchio-oto-renal syndrome.The link can be explained by structural and functional similarities between tissues in the inner ear and in the kidney. Also, toxins that accumulate in kidney failure can damage nerves, including those in the inner ear.Goal. To study the causes, clinical manifestations of Branchio-oto-renal (BOR) syndrome. Materials and Methods. Review of modern and foreign literary sources; methods - description, analysis, abstracting.Results and discussion. Mutations in three genes, EYA1, SIX1, and SIX5, have been reported in people with BOR/BO syndrome. About 40 percent of people with this condition have a mutation in the EYA1 gene. SIX1 gene mutations are a much less common cause of the disorder. SIX5 gene mutations have been found in a small number of people with BOR syndrome, although researchers question whether mutations in this gene cause the condition. Some affected individuals originally reported to have SIX5 gene mutations were later found to have EYA1 gene mutations as well, and researchers suspect that the EYA1 gene mutations may be the actual cause of the condition in these people.The proteins produced from the EYA1, SIX1, and SIX5 genes play important roles in development before birth. The EYA1 protein interacts with several other proteins, including SIX1 and SIX5, to regulate the activity of genes involved in many aspects of embryonic development. Research suggests that these protein interactions are essential for the normal formation of many organs and tissues, including the second branchial arch, ears, and kidneys. Mutations in the EYA1, SIX1, or SIX5 gene may disrupt the proteins’ ability to interact with one another and regulate gene activity.Conclusions. The link between ear anomalies and kidney function can be explained by structural and functional similarities between tissues in the inner ear and in the kidney. Additionally, toxins that accumulate in kidney failure can damage nerves, including those in the inner ear.

A study of the anatomical variations in branching pattern of middle cerebral artery

Middle cerebral artery (MCA) is the largest and most complex arterial system of the brain. Variations of the aortic arch branches are due to alteration in the development of specific branchial arch arteries during the embryonic period. Knowledge of these variations is important during aortic instrumentation, thoracic, and neck surgeries. The anatomy of the anterior cerebral artery branches and the anterior communicating artery complex needs to be investigated individually to minimise neurovascular morbidity before iatrogenic procedures. The study aimed to study the variations in the microsurgical anatomy of the MCA in our population and compare the variables and discuss their importance with anatomic and surgical considerations. Specimens were collected from the embalmed cadavers and the post-mortem bodies in the department of forensic medicine of Thanjavur Medical College. The different variables regarding the MCA in our population were analysed and compared with the studies in the Western population and other Indian studies. The mean length of the MCA in this study was 12.8 mm with a standard error of 3.79 mm. The outer diameter of the M1 segment was with a mean length of 3.75mm. In 69.2% middle, Cerebral Artery shows bifurcation and in 20%, it shows trifurcation and in 10.8%, it shows ramification types of branching patterns. The 39.1% cases show Temporo polar, 21.7% orbitofrontal, 9.1% anterior temporal, 6.6% prefrontal, and 4.1% middle temporal branches. Our results also reveal that the origin of the lenticulostriate branch in the middle cerebral artery was 85.85% from the trunk and 14.2% from division, respectively. MCA branching pattern is slightly higher in trifurcation pattern as compared to bifurcation and ramification. Thorough knowledge of the microvascular anatomy and the myriads of variations is essential for the operating surgeon to choose the ideal technique to avoid any catastrophe during and after surgery and give the best possible functional outcome.

Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling

The first and second branchiomeric (branchial arch) muscles are craniofacial muscles that derive from branchial arch mesoderm. In mammals, this set of muscles is indispensable for jaw movement and facial expression. Defects during embryonic development that result in congenital partial absence of these muscles can have significant impact on patients’ quality of life. However, the detailed molecular and cellular mechanisms that regulate branchiomeric muscle development remains poorly understood. Herein we investigated the role of retinoic acid (RA) signaling in developing branchiomeric muscles using mice as a model. We administered all-trans RA (25 mg/kg body weight) to Institute of Cancer Research (ICR) pregnant mice by gastric intubation from E8.5 to E10.5. In their embryos at E13.5, we found that muscles derived from the first branchial arch (temporalis, masseter) and second branchial arch (frontalis, orbicularis oculi) were severely affected or undetectable, while other craniofacial muscles were hypoplastic. We detected elevated cell death in the branchial arch mesoderm cells in RA-treated embryos, suggesting that excessive RA signaling reduces the survival of precursor cells of branchiomeric muscles, resulting in the development of hypoplastic craniofacial muscles. In order to uncover the signaling pathway(s) underlying this etiology, we focused on Pitx2, Tbx1, and MyoD1, which are critical for cranial muscle development. Noticeably reduced expression of all these genes was detected in the first and second branchial arch of RA-treated embryos. Moreover, elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of Pitx2, Tbx1, MyoD1, and Dlx5/6, and reduced survival of cranial myogenic precursor cells.