Pharyngeal Pouch Research Articles

Our experience: Pharyngeal Pouches, a Multimodal Approach to Treatment Under a Single Anaesthetic. A Retrospective Analysis of a Cohort of 105 Cases.

Our experience: Pharyngeal Pouches, a Multimodal Approach to Treatment Under a Single Anaesthetic. A Retrospective Analysis of a Cohort of 105 Cases.

Periderm fate and independence of tooth formation are conserved across osteichthyans

BackgroundPrevious studies have reported that periderm (the outer ectodermal layer) in zebrafish partially expands into the mouth and pharyngeal pouches, but does not reach the medial endoderm, where the pharyngeal teeth develop. Instead, periderm-like cells, arising independently from the outer periderm, cover prospective tooth-forming epithelia and are crucial for tooth germ initiation. Here we test the hypothesis that restricted expansion of periderm is a teleost-specific character possibly related to the derived way of early embryonic development. To this end, we performed lineage tracing of the periderm in a non-teleost actinopterygian species possessing pharyngeal teeth, the sterlet sturgeon (Acipenser ruthenus), and a sarcopterygian species lacking pharyngeal teeth, the axolotl (Ambystoma mexicanum).ResultsIn sturgeon, a stratified ectoderm is firmly established at the end of gastrulation, with minimally a basal ectodermal layer and a surface layer that can be homologized to a periderm. Periderm expands to a limited extent into the mouth and remains restricted to the distal parts of the pouches. It does not reach the medial pharyngeal endoderm, where pharyngeal teeth are located. Thus, periderm in sturgeon covers prospective odontogenic epithelium in the jaw region (oral teeth) but not in the pharyngeal region. In axolotl, like in sturgeon, periderm expansion in the oropharynx is restricted to the distal parts of the opening pouches. Oral teeth in axolotl develop long before mouth opening and possible expansion of the periderm into the mouth cavity.ConclusionsRestricted periderm expansion into the oropharynx appears to be an ancestral feature for osteichthyans, as it is found in sturgeon, zebrafish and axolotl. Periderm behavior does not correlate with presence or absence of oral or pharyngeal teeth, whose induction may depend on ‘ectodermalized’ endoderm. It is proposed that periderm assists in lumenization of the pouches to create an open gill slit. Comparison of basal and advanced actinopterygians with sarcopterygians (axolotl) shows that different trajectories of embryonic development converge on similar dynamics of the periderm: a restricted expansion into the mouth and prospective gill slits.

Characterisation of Kürsteiner canals of parathyroid: imparting relevance to a one-and-a-quarter-century-old concept.

Kürsteiner canals (KC) were described at least 125 years ago as pharyngeal pouch embryological remnants of parathyroid and thymic development. While considered precursors for a subset of parathyroid cysts and salivary heterotopias (SH), they remain enigmatic. We now define a comprehensive phenotype of KC remnants and investigate their role in a spectrum of parathyroid lesions. `Sixty-two cystic and 22 non-cystic parathyroid lesions (73 patients) were retrieved from our institutional archive (2011-23) and evaluated for the presence of KC and prevalence of KC phenotype in parathyroid hormone (PTH)-positive and PTH-negative cysts. KC phenotype was defined as: cysts and tubules with surrounding sclerosis; bland, unilayered lining with frequent nuclear indentation of lumina; vesicular chromatin relative to chief cells; attenuated eosinophilic to 'hyper-cleared' cytoplasm; and staining pattern PTH-negative, SOX-10-positive, CK7-positive, GATA-3-positive and PAX-9 dim, a subset with oestrogen/progesterone receptor (ER/PR) positivity. Thirty PTH-negative cysts were identified in the neck/mediastinum; 14 of this group also showed SH. Thirty-two PTH-positive cysts included: 11 cystic parathyroid adenomas, 17 hyperplastic parathyroids, and four carcinomas. KC showed two distinct subtypes and were often found near PTH-negative cysts. PTH-negative cysts were associated with inferior parathyroids, SOX-10 positivity, fibrosclerosis, vesicular nuclei indenting cyst lumina and hyper-cleared or attenuated eosinophilic cytoplasm. KC are common in parathyroids and show a distinct histological and immunohistochemical profile, with an inferior predilection favouring branchial cleft III distribution. Diagnostically, the high prevalence of this phenotype in PTH-negative cysts and salivary heterotopia supports derivation of non-functioning cysts from KC. Conversely, PTH-positive cysts are more compatible with cystic change within hyperfunctioning glands.

Management of a Piriform Sinus Fistula With Chronic Neck Infection in an Adult.

A pyriform sinus fistula (PSF) is a rare congenital anomaly due to failed obliteration of the third or fourth pharyngeal pouch. Diagnosis and management of PSF remains controversial. We present a case of PSF and discuss its diagnosis and management. Case report and literature review. A 26-year-old female with a chronic left lateral neck abscess was diagnosed with a left PSF. She underwent surgery through a combined approach to close the openings of the PSF, internally and externally. We first placed a blunted ET tube into the internal opening of the PSF. We then performed an external transcervical approach to close the PSF at the cricothyroid membrane. Briefly, after a neck debridement and washout of the chronic neck infection, we identified the recurrent laryngeal nerve (RLN) in Lore's triangle. We performed left hemithyroidectomy to facilitate the dissection and protection of the RLN to its entrance into the larynx. A flexible laryngoscope was then inserted into the left piriform sinus through the ET tube to guide external dissection by transillumination. The scar tissue attached to the superior pole of the left thyroid lobe was then ligated and divided along the cricothyroid membrane. Lastly, we cauterized the internal opening of the PSF. The patient has remained recurrence-free for 1.5 years with normal vocal cord mobility. Histopathology revealed presence of a squamous-lined tract adjacent to the thyroid tissue. Surgical treatment for patients with PSF should be aimed at closing the internal and external openings of the PSF, debriding chronic neck infection, and protecting the laryngeal nerves, instead of removing the entire tract. A concurrent hemithyroidectomy facilitates the identification and protection of the RLN, as well as excision of the tract. Differentiation between third and fourth branchial cleft fistulae may not be clinically necessary, as it is unlikely to alter the therapeutic plan.

359. INNOVATIVE USE OF WEERDA DIVERTICULOSCOPE FOR REMOVAL OF AN IMPACTED SHARP FOREIGN BODY IN THE CERVICAL OESOPHAGUS MIMICKING MALIGNANCY

Abstract Background Chronically impacted sharp foreign bodies (FB) of the cervical or upper thoracic oesophagus can present a diagnostic dilemma. Fifty percent of sharp objects tend to lodge in the upper oesophagus and frequently cause perforation. A multidisciplinary approach is warranted. Eventually, surgery by cervical oesophagotomy/thoracotomy may be required. The Weerda diverticuloscope offers excellent endoscopic visibility and access to the lumen of the upper oesophagus allowing for removal of FBs and mitigating risks of a major surgical procedure. Methods We report an interesting case of a 27 year old gentleman being investigated for dysphagia. The patient notes were obtained from the electronic patient records. The radiological images were sourced from the picture archiving and communication system (PACS) and endoscopy from stored images. The patient was radiologically diagnosed as having T4 malignancy but consecutive biopsies suggested Actinomycosis. Patient thereafter recollected having a fist fight and losing his dentures. This triggered the use of the Weerda diverticuloscope, a bivalved rigid diverticuloscope (Karl Storz, Tuttlingen, Germany). It has a distal fibreoptic illumination that is designed for trans-oral stapling of pharyngeal pouches Results Under general anaesthesia, the Weerda diverticuloscope was introduced into the cervical oesophagus. The tips of the jaws positioned just proximal to the embedded dental prosthesis. The diverticuloscope was suspended for stabilisation in the same manner as for endoscopic stapling of a pharyngeal pouch and the jaws were distracted to allow endoscopic access. A 5mm rigid telescope was passed alongside a pair of heavy endoscopic scissors and the prosthesis was divided into 3 parts. The central intraluminal component was removed first using endoscopic forceps, followed by gentle disimpaction and extraction of the remaining two components embedded in the oesophageal wall. Conclusion Foreign bodies in the oesophagus rarely can mimic cancer or chronic granulomatous diseases. A multidisciplinary approach is occassionally recommended in their management. There have been a few published reports of the use of the Weerda diverticuloscope to remove upper oesophageal FBs successfully. It’s use, however, is not often considered routinely. We recommend the use of this technique at centres where expertise in endoscopic management of Zenker’s diverticula is available and when endoscopic retrieval has failed.

A Potential Role of fgf4, fgf24, and fgf17 in Pharyngeal Pouch Formation in Zebrafish.

In vertebrates, Fgf signaling is essential for the development of pharyngeal pouches, which controls facial skeletal development. Genetically, fgf3 and fgf8 are required for pouch formation in mice and zebrafish. However, loss-of-function phenotypes of fgf3 and fgf8 are milder than expected in mice and zebrafish, which suggests that an additional fgf gene(s) would be involved in pouch formation. Here, we analyzed the expression, regulation, and function of three fgfs, fgf4, fgf24, and fgf17, during pouch development in zebrafish. We find that they are expressed in the distinct regions of pharyngeal endoderm in pouch formation, with fgf4 and fgf17 also being expressed in the adjacent mesoderm, in addition to previously reported endodermal fgf3 and mesodermal fgf8 expression. The endodermal expression of fgf4, fgf24, and fgf17 and the mesodermal expression of fgf4 and fgf17 are positively regulated by Tbx1 but not by Fgf3, in pouch formation. Fgf8 is required to express the endodermal expression of fgf4 and fgf24. Interestingly, however, single mutant, all double mutant combinations, and triple mutant for fgf4, fgf24, and fgf17 do not show any defects in pouches and facial skeletons. Considering a high degree of genetic redundancy in the Fgf signaling components in craniofacial development in zebrafish, our result suggests that fgf4, fgf24, and fgf17 have a potential role for pouch formation, with a redundancy with other fgf gene(s).

HOXA3 functions as the on-off switch to regulate the development of hESC-derived third pharyngeal pouch endoderm through EPHB2-mediated Wnt pathway.

Normal commitment of the endoderm of the third pharyngeal pouch (3PP) is essential for the development and differentiation of the thymus. The aim of this study was to investigate the role of transcription factor HOXA3 in the development and differentiation of 3PP endoderm (3PPE) from human embryonic stem cells (hESCs). The 3PPE was differentiated from hESC-derived definitive endoderm (DE) by mimicking developmental queues with Activin A, WNT3A, retinoic acid and BMP4. The function of 3PPE was assessed by further differentiating into functional thymic epithelial cells (TECs). The effect of HOXA3 inhibition on cells of 3PPE was subsequently investigated. A highly efficient approach for differentiating 3PPE cells was developed and these cells expressed 3PPE related genes HOXA3, SIX1, PAX9 as well as EpCAM. 3PPE cells had a strong potential to develop into TECs which expressed both cortical TEC markers K8 and CD205, and medullary TEC markers K5 and AIRE, and also promoted the development and maturation of T cells. More importantly, transcription factor HOXA3 not only regulated the differentiation of 3PPE, but also had a crucial role for the proliferation and migration of 3PPE cells. Our further investigation revealed that HOXA3 controlled the commitment and function of 3PPE through the regulation of Wnt signaling pathway by activating EPHB2. Our results demonstrated that HOXA3 functioned as the on-off switch to regulate the development of hESC-derived 3PPE through EPHB2-mediated Wnt pathway, and our findings will provide new insights into studying the development of 3PP and thymic organ in vitro and in vivo.

Cases of Digeorge Syndrome

Abstract DiGeorge syndrome is a primary immunodeficiency caused by the abnormal growth of the third and fourth pharyngeal pouches throughout prenatal development. It is typified by a triad: hypocalcemia due to hypoparathyroidism, some heart defects, and thymic hypoplasia or aplasia. This syndrome is associated with a microdeletion in the chromosomal region 22q11.2. DiGeorge syndrome together with other dysfunctions like velo-cardio-facial syndrome and Takao syndrome have overlapping traits. The symptoms are hidden under the name CATCH22. It describes signs like a cardiac defect, abnormal facies, thyme hypoplasia, cleft palate, hypocalcemia, and chromosome 22q11.2 deletions. Its incidence is estimated to be approximately 1:3000 live births. The disorder is inherited in an autosomal dominant pattern or arises from de novo mutation. 22q11.2 microdeletion is associated with an increased risk of developing mental diseases, including schizophrenia. In the general population, 1-2% of people suffer from schizophrenia. In DiGeorge syndrome this ratio is much higher, around 25-30%. Nowadays, the fluorescence in situ hybridization (FISH) is a gold standard method for the diagnosis of microdeletion syndrome. Currently, there is no effective therapy to prevent the development of the disease.

Fgf signalling is required for gill slit formation in the skate, Leucoraja erinacea

The gill slits of fishes develop from an iterative series of pharyngeal endodermal pouches that contact and fuse with surface ectoderm on either side of the embryonic head. We find in the skate (Leucoraja erinacea) that all gill slits form via a stereotypical sequence of epithelial interactions: 1) endodermal pouches approach overlying surface ectoderm, with 2) focal degradation of ectodermal basement membranes preceding endoderm–ectoderm contact; 3) endodermal pouches contact and intercalate with overlying surface ectoderm, and finally 4) perforation of a gill slit occurs by epithelial remodelling, without programmed cell death, at the site of endoderm–ectoderm intercalation. Skate embryos express Fgf8 and Fgf3 within developing pharyngeal epithelia during gill slit formation. When we inhibit Fgf signalling by treating skate embryos with the Fgf receptor inhibitor SU5402 we find that endodermal pouch formation, basement membrane degradation and endodermal–ectodermal intercalation are unaffected, but that epithelial remodelling and gill slit perforation fail to occur. These findings point to a role for Fgf signalling in epithelial remodelling during gill slit formation in the skate and, more broadly, to an ancestral role for Fgf signalling during pharyngeal pouch epithelial morphogenesis in vertebrate embryos.

OGBN P19 Innovative use of Weerda diverticuloscope for removal of an impacted sharp foreign body mimicking malignancy in the cervical oesophagus

Abstract Background Chronically impacted sharp foreign bodies (FB) of the cervical or upper thoracic oesophagus can present a diagnostic dilemma .Fifty percent of sharp objects tend to lodge in the upper oesophagus and frequently cause perforation.A multidisciplinary approach is warranted. Eventually, surgery by cervical oesophagotomy/thoracotomy may be required. The Weerda diverticuloscope offers excellent endoscopic visibility and access to the lumen of the upper oesophagus allowing for removal of FBs and mitigating risks of a major surgical procedure. Methods We report an interesting case of a 27 year old gentleman being investigated for dysphagia. The patient was radiologically diagnosed as having T4 malignancy but consecutive biopsies suggested Actinomycosis. Patient interestingly recollected having lost his dentures after a fist fight. This triggered the use of the Weerda diverticuloscope, a bivalved rigid diverticuloscope ( Karl Storz, Tuttlingen, Germany). It has a distal fibreoptic illumination that is designed for trans-oral stapling of pharyngeal pouches.The patient notes were obtained from the electronic patient records. The radiological images were sourced from the picture archiving and communication system (PACS) and endoscopy from stored images. Results Under general anaesthesia, the Weerda diverticuloscope was introduced into the cervical oesophagus .The tips of the jaws positioned just proximal to the embedded dental prosthesis. The diverticuloscope was suspended for stabilisation in the same manner as for endoscopic stapling of a pharyngeal pouch and the jaws were distracted to allow endoscopic access. A 5mm rigid telescope was passed alongside a pair of heavy endoscopic scissors and the prosthesis was divided into 3 parts. The central intraluminal component was removed first using endoscopic forceps, followed by gentle disimpaction and extraction of the remaining two components embedded in the oesophageal wall. Conclusions Chronically impacted FBs in the oesophagus can rarely mimic cancer or chronic granulomatous diseases. A multidisciplinary approach is occassionally recommended in their management. There have been a few published reports of the use of the Weerda diverticuloscope to remove upper oesophageal FBs successfully. It’s use, however,is not often considered routinely. We recommend the use of this technique at centres where expertise in endoscopic management of Zenker’s diverticula is available and when endoscopic retrieval has failed.

Tmem88 plays an essential role in pharyngeal pouch progenitor specification by inhibiting Wnt/β-catenin signaling

Abstract Pharyngeal pouches, which are endodermal outpockets that segment the pharyngeal arches, play a crucial role in the development of craniofacial skeletons in vertebrate embryos. Our previous study successfully identified pharyngeal pouch progenitors (PPPs) in zebrafish embryos and emphasized the significance of BMP2b signaling in their specification. However, the specific mechanism by which these progenitors originate from endodermal cells remains largely unknown. Here we found that the pharmacological activation of Wnt signaling pathway disrupts the emergence of PPPs and subsequently hinders the formation of pharyngeal pouches. Moreover, we have identified the expression of tmem88a and tmem88b (collectively known as tmem88a/b) in PPPs during the early-somite stages. Furthermore, the deficiency of tmem88a/b leads to an excessive accumulation of β-catenin in both the cytoplasm and nucleus of endodermal cells that are intended to differentiate into PPPs. Importantly, suppressing the hyperactivation of Wnt/β-catenin signaling through pharmacological treatment, the defects in PPP specification in tmem88a/b−/− mutants are successfully rescued. In summary, our findings establish a clear connection between the specification of PPPs and the regulation of Wnt signaling mediated by Tmem88. These results underscore the pivotal role of Tmem88 in the development of pharyngeal pouches.

Cxcl12a plays an essential role in pharyngeal cartilage development.

Background: Neural crest cells constitute a distinct set of multipotent cells that undergo migration along predefined pathways, culmination in the differentiation into a plethora of cell types, including components of the pharyngeal cartilage. The neurocranium is composite structure derived from both cranial neural crest and mesoderm cells, whereas the pharyngeal skeletal elements-including the mandibular and branchial arches-are exclusively formed by craniofacial neural crest cells. Previous studies have elucidated the critical involvement of the chemokine signaling axis Cxcl12b/Cxcr4a in craniofacial development in zebrafish (Danio rerio). Nonetheless, the function contribution of Cxcl12a and Cxcr4b-the homologous counterparts of Cxcl12b and Cxcr4a-remain largely unexplored. Methods: In the present study, mutant lines for cxcl12a and cxcr4b were generated employing CRISPR/Cas9 system. Temporal and spatial expression patterns of specific genes were assessed using in situ hybridization and dual-color fluorescence in situ hybridization techniques. High-resolution confocal microscopy was utilized for in vivo imaging to detect the pharyngeal arch or pouch patterning. Additionally, cartilage formation within the craniofacial region was analyzed via Alcian blue staining, and the proliferation and apoptosis rates of craniofacial neural crest cells were quantified through BrdU incorporation and TUNEL staining. Results: Our data reveals that the deletion of the chemokine gene cxcl12a results in a marked diminution of pharyngeal cartilage elements, attributable to compromised proliferation of post-migratory craniofacial neural crest cells. Subsequent experiments confirmed that Cxcl12a and Cxcl12b exhibit a synergistic influence on pharyngeal arch and pouch formation. Conclusion: Collectively, the present investigation furnishes compelling empirical evidence supporting the indispensable role of Cxcl2a in craniofacial cartilage morphogenesis, albeit cxcr4b mutants exert a minimal impact on this biological process. We delineate that Cxcl12a is essential for chondrogenesis in zebrafish, primarily by promoting the proliferation of craniofacial neural crest cells. Furthermore, we proposed a conceptual framework wherein Cxcl12a and Cxcl12b function synergistically in orchestrating both the pharyngeal arch and pouch morphogenesis.

Pre-mandibular pharyngeal pouches in early non-teleost fish embryos.

The vertebrate pharynx is a key embryonic structure with crucial importance for the metameric organization of the head and face. The pharynx is primarily built upon progressive formation of paired pharyngeal pouches that typically develop in post-oral (mandibular, hyoid and branchial) domains. However, in the early embryos of non-teleost fishes, we have previously identified pharyngeal pouch-like outpocketings also in the pre-oral domain of the cranial endoderm. This pre-oral gut (POG) forms by early pouching of the primitive gut cavity, followed by the sequential formation of typical (post-oral) pharyngeal pouches. Here, we tested the pharyngeal nature of the POG by analysing expression patterns of selected core pharyngeal regulatory network genes in bichir and sturgeon embryos. Our comparison revealed generally shared expression patterns, including Shh, Pax9, Tbx1, Eya1, Six1, Ripply3 or Fgf8, between early POG and post-oral pharyngeal pouches. POG thus shares pharyngeal pouch-like morphogenesis and a gene expression profile with pharyngeal pouches and can be regarded as a pre-mandibular pharyngeal pouch. We further suggest that pre-mandibular pharyngeal pouches represent a plesiomorphic vertebrate trait inherited from our ancestor's pharyngeal metameric organization, which is incorporated in the early formation of the pre-chordal plate of vertebrate embryos.

Idiopathic Palatal Fistula of the Left Soft Palate.

Palatal fistulas, often congenital or trauma-induced, are occasionally encountered in the field of plastic surgery. We report a case of a non-medial 3mm soft palate fistula in a 43-year-old woman, with no apparent trigger or history of local trauma or infection. The fistula, extending 2cm toward the lateral pharyngeal wall, was surgically removed under general anesthesia as it was impacting the patient's quality of life. The lumen was stained, and the fistula was removed in one mass. The excised tissue was covered with stratified squamous epithelium and was surrounded by adherent tonsil tissue. No recurrence was observed postoperatively. Despite an initial suspicion of a congenital cause, the fistula's lateral extension and histology suggested a possible origin from the second pharyngeal pouch. To date, there are no reports of fistulas opening on the soft palate. Therefore, this presents an exceptionally rare instance of a soft palate fistula.

Foxi3GFP and Foxi3CreER mice allow identification and lineage labeling of pharyngeal arch ectoderm and endoderm, and tooth and hair placodes.

FOXI3 is a forkhead family transcription factor that is expressed in the progenitors of craniofacial placodes, epidermal placodes, and the ectoderm and endoderm of the pharyngeal arch region. Loss of Foxi3 in mice and pathogenic Foxi3 variants in dogs and humans cause a variety of craniofacial defects including absence of the inner ear, severe truncations of the jaw, loss or reduction in external and middle ear structures, and defects in teeth and hair. To allow for the identification, isolation, and lineage tracing of Foxi3-expressing cells in developing mice, we targeted the Foxi3 locus to create Foxi3GFP and Foxi3CreER mice. We show that Foxi3GFP mice faithfully recapitulate the expression pattern of Foxi3 mRNA at all ages examined, and Foxi3CreER mice can trace the derivatives of pharyngeal arch ectoderm and endoderm, the pharyngeal pouches and clefts that separate each arch, and the derivatives of hair and tooth placodes. Foxi3GFP and Foxi3CreER mice are new tools that will be of use in identifying and manipulating pharyngeal arch ectoderm and endoderm and hair and tooth placodes.

Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis.

During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population as mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in the understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells.

Cellular and molecular mechanisms of the organogenesis and development, and function of the mammalian parathyroid gland.

Serum calcium homeostasis is mainly regulated by parathormone (PTH) secreted by the parathyroid gland. Besides PTH and Gcm2, a master gene for parathyroid differentiation, many genes are expressed in the gland. Especially, calcium-sensing receptor (CaSR), vitamin D receptor (VDR), and Klotho function to prevent increased secretion of PTH and hyperplasia of the parathyroid gland under chronic hypocalcemia. Parathyroid-specific dual deletion of Klotho and CaSR induces a marked enlargement of the glandular size. The parathyroid develops from the third and fourth pharyngeal pouches except murine species in which the gland is derived from the third pouch only. The development of the murine parathyroid gland is categorized as follows: (1) formation and differentiation of the pharyngeal pouches, (2) appearance of parathyroid domain in the third pharyngeal pouch together with thymus domain, (3) migration of parathyroid primordium attached to the top of thymus, and (4) contact with the thyroid lobe and separation from the thymus. The transcription factors and signaling molecules involved in each of these developmental stages are elaborated. In addition, mesenchymal neural crest cells surrounding the pharyngeal pouches and parathyroid primordium and invading the parathyroid parenchyma participate in the development of the gland.

Case report – A rare syndromic association (Goldenhar syndrome)

ABSTRACT Goldenhar syndrome is a diverse and poorly understood continuum of disorders of unknown etiology. It is a complex of developmental disorders (face, ears, eyes, spine, etc.), varying in severity in each patient. The estimated incidence of the syndrome ranges from 1 in 3500 to 5600 live births. The male-to-female ratio is approximately 3:2. Most cases of Goldenhar syndrome occur sporadically, although several case reports have documented occurrences in successive generations that require consideration of autosomal recessive, dominant, or multifactorial inheritance. Since there are other syndromes with similar features, there is still confusion regarding which cases should be classified specifically as Goldenhar syndrome. Goldenhar syndrome is a malformation complex of varying severity, involving the structures arising from the first and second branchial arches, the first pharyngeal pouch, the first branchial cleft and the primordia of the temporal bone. We are presenting a rare case of 2 ½ months old male, with asymmetry of the frontonasal area, left auricle anotia, preauricular tags, epicanthus, and left facial nerve palsy. The child had thoracic hemivertebra and fused right ectopic kidney on left side with grade IV VUR. The child had H type trachea esophageal fistula which was confirmed on CT thorax which was a cause of recurrent chest infections in child.

Patterns of senescence and apoptosis during development of branchial arches, epibranchial placodes, and pharyngeal pouches.

Many developmental processes are coregulated by apoptosis and senescence. However, there is a lack of data on the development of branchial arches, epibranchial placodes, and pharyngeal pouches, which harbor epibranchial signaling centers. Using immunohistochemical, histochemical, and 3D reconstruction methods, we show that in mice, senescence and apoptosis together may contribute to the invagination of the branchial clefts and the deepening of the cervical sinus floor, in antagonism to the proliferation acting in the evaginating branchial arches. The concomitant apoptotic elimination of lateral line rudiments occurs in the absence of senescence. In the epibranchial placodes, senescence and apoptosis appear to (1) support invagination or at least indentation by immobilizing the margins of the centrally proliferating pit, (2) coregulate the number and fate of Pax8+ precursors, (3) progressively narrow neuroblast delamination sites, and (4) contribute to placode regression. Putative epibranchial signaling centers in the pharyngeal pouches are likely deactivated by rostral senescence and caudal apoptosis. Our results reveal a plethora of novel patterns of apoptosis and senescence, some overlapping, some complementary, whose functional contributions to the development of the branchial region, including the epibranchial placodes and their signaling centers, can now be tested experimentally.

Imaging Features of Ectopic Tissues and Their Complications: Embryologic and Anatomic Approach

Ectopic tissue is an anatomic abnormality in which tissue develops in an area outside its normal location. It is primarily caused by abnormalities during the process of embryologic development. Although the majority of individuals with ectopic tissues remain asymptomatic, various symptoms and associated complications can occur. Failure in normal embryologic development leads to loss of normal physiologic function or may result in harmful functions such as ectopic hormonal secretion in the ectopic pituitary adenoma. Ectopic tissues may also frequently mimic tumors. For example, developmental abnormalities in the pharyngeal pouches may result in an ectopic parathyroid gland and ectopic thymus, both of which are frequently misdiagnosed as tumors. Adequate knowledge of embryology is essential for understanding the differential diagnoses of ectopic tissues and facilitating appropriate management. The authors summarize the embryologic development and pathogenesis of ectopic tissues by using illustrations to facilitate a deeper understanding of embryologic development and anatomy. Characteristic imaging findings (US, CT, MRI, and scintigraphy) are described for ectopic tissues of the brain, head, neck, thorax, abdomen, and pelvis by focusing on common conditions that radiologists may encounter in daily practice and their differential diagnoses. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.