Multiciliated cells (MCCs) are specialized epithelia with apical bundles of motile cilia that direct fluid flow. MCC dysfunction is associated with human diseases of the respiratory, reproductive, and central nervous systems. Further, the appearance of renal MCCs has been cataloged in several kidney conditions, where their function is unknown. Despite their pivotal health importance, many aspects of MCC development remain poorly understood. Here, we utilized a chemical screen to identify molecules that affect MCC ontogeny in the zebrafish embryo kidney, and found prostaglandin signaling is essential both for renal MCC progenitor formation and terminal differentiation. Moreover, we show that prostaglandin activity is required downstream of the transcription factorets variant 5a(etv5a) during MCC fate choice, where modulating prostaglandin E2(PGE2) levels rescued MCC number. The discovery that prostaglandin signaling mediates renal MCC development has broad implications for other tissues, and could provide insight into a multitude of pathological states.

In recent years, the zebrafish embryo has emerged as a popular model to study developmental biology due to traits such as ex utero embryo development and optical transparency. In particular, the zebrafish embryo has become an important organism to study vertebrate kidney organogenesis as well as multiciliated cell (MCC) development. To visualize MCCs in the embryonic zebrafish kidney, we have developed a combined protocol of whole-mount fluorescent in situ hybridization (FISH) and whole mount immunofluorescence (IF) that enables high resolution imaging. This manuscript describes our technique for co-localizing RNA transcripts and protein as a tool to better understand the regulation of developmental programs through the expression of various lineage factors.

Knowledge about the genetic pathways that control nephron development is essential for better understanding the basis of congenital malformations of the kidney. The transcription factors Osr1 and Hand2 are known to exert antagonistic influences to balance kidney specification. Here, we performed a forward genetic screen to identify nephrogenesis regulators, where whole genome sequencing identified an osr1 lesion in the novel oceanside (ocn) mutant. The characterization of the mutant revealed that osr1 is needed to specify not renal progenitors but rather their maintenance. Additionally, osr1 promotes the expression of wnt2ba in the intermediate mesoderm (IM) and later the podocyte lineage. wnt2ba deficiency reduced podocytes, where overexpression of wnt2ba was sufficient to rescue podocytes and osr1 deficiency. Antagonism between osr1 and hand2 mediates podocyte development specifically by controlling wnt2ba expression. These studies reveal new insights about the roles of Osr1 in promoting renal progenitor survival and lineage choice.

Background: The biceps superior labral complex is a known source of shoulder dysfunction in young, high-level athletes. Superior labral anterior-posterior (SLAP) repairs are often unsatisfactory for treating biceps-labral pathology in this demographic group, with high failure rates and poor return to sport (RTS). Minimal data have been published to demonstrate patient-reported outcomes (PROs) and RTS in gymnasts after treatment of SLAP pathologies. Hypothesis: Gymnasts undergoing biceps tenodesis for SLAP pathologies would have satisfactory PROs and satisfactory RTS. Study Design: Case series; Level of evidence, 4. Methods: Gymnasts aged ≤25 years who underwent open subpectoral biceps tenodesis for SLAP tears with or without biceps tendon pathology between August 20, 2014, and August 20, 2019, and who had minimum 2-year follow-up data were included in this study. Tenodesis was performed using a subpectoral technique with bicortical button fixation. The following PROs were included: RTS, postoperative activity level, 10-point visual analog scale for pain (VAS–Pain), American Shoulder and Elbow Surgeons (ASES), and Disabilities of the Arm, Shoulder and Hand (DASH) scores. Results: Of 16 shoulders in 14 gymnasts undergoing biceps tenodesis for SLAP tear during the study period, a follow-up was obtained for 13 of 16 shoulders (81%) at 4.3 ± 1.5 years. The mean age of patients at the time of surgery was 21.8 ± 2.2 years, with 12 (92%) male patients. Biceps tenodesis was performed as the primary procedure for the diagnosis of SLAP tear in 12 patients (92%) and for failed prior SLAP repair in 1 patient (8%). PROs were excellent at the follow-up, with VAS–Pain scores of 1.8 ± 1.7, ASES scores of 89.1 ± 9.1, and DASH scores of 2.4 ± 3.2. After surgery, 8 (62%) patients returned to their prior level of collegiate gymnastics. Three (60%) of 5 patients did not return to collegiate gymnastics because of the end of eligibility, and 2 (40%) patients did not return to collegiate gymnastics because of knee injuries. Significantly higher DASH scores were noted in the group that did not RTS ( P = .04). No patients experienced postoperative complications or reoperation. Conclusion: Biceps tenodesis was an effective primary operation for high-level gymnasts with SLAP tears, with a satisfactory rate of return to the same level of sport and excellent PROs.

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