Nkd1, a negative feedback regulator of the Wnt pathway, localizes with Dvl2 to the putative Wnt signalosome, where it becomes activated by Wnt. Activated Nkd1 moves away from the membrane to become more cytosolic, where it interacts with β-catenin to prevent nuclear accumulation.

Settlement is a rapid process in many marine invertebrate species, transitioning a planktonic larva into a benthic juvenile. In indirectly developing sea urchins, this ecological transition correlates with a morphological, developmental and physiological transition (metamorphosis) during which apoptosis is essential for the resorption and remodelling of larval and juvenile structures. While settlement is initiated by environmental cues (i.e. habitat-specific or benthic substrate cues), metamorphosis is regulated by developmental endocrine signals, such as histamine (HA), thyroid hormones (THs) and nitric oxide (NO). In the purple sea urchin, Strongylocentrotus purpuratus, we found that suH1R mRNA levels increase during larval development and peak during metamorphic competence. SuH1R positive cell clusters are prominently visible in the mouth region of sea urchin larvae, but the protein appears to be expressed at low levels throughout the larval arms and epidermis. SuH1R knock-down experiments in larval stages show that the function of suH1R is in inhibiting apoptosis. Our results therefore suggest that suH1R is regulating the metamorphic transition by inhibiting apoptosis. These results provide new insights into metamorphic mechanisms and have implications for our understanding of settlement and metamorphosis in the marine environment.

The mammalian dentition is a serially homogeneous structure that exhibits wide numerical and morphological variation among multiple different species. Patterning of the dentition is achieved through complex reiterative molecular signaling interactions that occur throughout the process of odontogenesis. The secreted signaling molecule Sonic hedgehog (Shh) plays a key role in this process, and the Shh coreceptor growth arrest-specific 1 (Gas1) is expressed in odontogenic mesenchyme and epithelium during multiple stages of tooth development. We show that mice engineered with Gas1 loss-of-function mutation have variation in number, morphology, and size of teeth within their molar dentition. Specifically, supernumerary teeth with variable morphology are present mesial to the first molar with high penetrance, while molar teeth are characterized by the presence of both additional and absent cusps, combined with reduced dimensions and exacerbated by the presence of a supernumerary tooth. We demonstrate that the supernumerary tooth in Gas1 mutant mice arises through proliferation and survival of vestigial tooth germs and that Gas1 function in cranial neural crest cells is essential for the regulation of tooth number, acting to restrict Wnt and downstream FGF signaling in odontogenic epithelium through facilitation of Shh signal transduction. Moreover, regulation of tooth number is independent of the additional Hedgehog coreceptors Cdon and Boc, which are also expressed in multiple regions of the developing tooth germ. Interestingly, further reduction of Hedgehog pathway activity in Shhtm6Amc hypomorphic mice leads to fusion of the molar field and reduced prevalence of supernumerary teeth in a Gas1 mutant background. Finally, we demonstrate defective coronal morphology and reduced coronal dimensions in the molar dentition of human subjects identified with pathogenic mutations in GAS1 and SHH/GAS1, suggesting that regulation of Hedgehog signaling through GAS1 is also essential for normal patterning of the human dentition.

Background?Single-photon emission computed tomography and computed tomography (SPECT/CT) is a hybrid diagnostic imaging modality that allows clinicians to integrate their diagnostic evaluations and deliver a definitive diagnosis in musculoskeletal disorders. Specifically, in identification of osseous pathology, the conventional bone scan delivers greater specificity compared with magnetic resonance imaging (MRI). However, use of SPECT/CT enhances the sensitivity and specificity. Use of this modality denotes the possibility to specify the lesion more accurately and precisely while grading the activity according to osseous structural changes. Purpose?This study aimed to evaluate the clinical utility of SPECT/CT in the diagnoses and management of osseous wrist disorders. The objectives were to examine the value of SPECT/CT in the diagnosis of osseous-related wrist pain and whether the findings altered management. Patients and Methods?A retrospective cohort study of 20 patients with such wrist pain was conducted. SPECT/CT was used in the diagnostic process for these patients. Results?Following SPECT/CT imaging, the common final diagnoses were osteoarthritis (10; 50%) and avascular necrosis (5; 25%). Less common diagnoses included ulnar carpal impact syndrome, infection, malunion, complex regional pain syndrome, and carpal boss. Some presented with multiple pathologies. SPECT/CT changed the final diagnosis in 11 cases, resulting in nonoperative treatment (7; 63%) or surgery (4; 37%). Conclusion?Findings from this study and the literature demonstrate the clinical utility of SPECT/CT in the assessment of osseous-related wrist disorders. We present an algorithm for the assessment of wrist pain with osseous pathology. This commences with clinical assessment and plane radiographs (first-line investigation). Some cases will require a second-line investigation (ultrasound, CT, and/or MRI). If the diagnosis remains unclear, SPECT/CT is recommended as a third-line investigation.

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