Abstract: SA-PO555

Robo2 Mediated Raldh2 Signaling in Bladder Mesenchyme Is Crucial for Ureter Development

Session Information

  • Developmental Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 401 Developmental Biology

Authors

  • Li, Qinggang, Chinese PLA general Hospital, Beijing, China
  • Chen, Xiangmei, Chinese PLA General Hospital, Beijing, BEIJING, China
Background

Congenital anomalies of urinary-tract are a significant cause of morbidity in infancy, many of the congenital anomalies are linked to ureter development. Despite the frequent occurrence of the ureter abnormalities, little is known about their cause that normally control ureter-bladder development.Robo2 loss can cause congenital abnormalities of the urinary-tract, with ureter defect and vesicoureteral reflux. While mechanistic aspects of this pathway are increasingly well defined, it remains unclear how Robo2 modulation impacts ureter development.

Methods

We performed in immunofluorescence on mouse embryonic whole mount kidney and section with E-cadherin ,and Co-IP and Mass spectrometry analysis on mouse embryonic kidneys and urogenital tracts with a specific ROBO2 polyclonal antibody. Laser scanning confocal microscopy and real time RT-PCR were used to observe expression of Robo2 in frozen section and urogenital tract samples. Kidney explants dissected from E12.5 embryo were cultured in DMEM/10%FCS.

Results

Robo2 is expressed in common nephric duct (CND) and primitive bladder, and interact with Raldh2. Moreover, the ureter elongation is depend on signaling in bladder, not kidney morphogenesis, reveals how Robo2 impact ureter cell fate decisions. Delayed apoptosis due to failure of CND fusion with primitive bladder in Robo2-/-embryo, resulting in the abnormal ureter remain connected to CND. Analysis of Robo2-/- mice reveals hydronephrosis and defective ureter development by the CND remodeling defects and delayed fusion with primitive bladder. Using retinoic acid rescued ureter anomalies in Robo2-/-embryo.

Conclusion

We found Robo2 impacts CND migration and fusion with primitive bladder via its novel protein partner Raldh2 signaling, this may have relevance for diverse disease conditions, associated with altered signaling from primitive bladder.

Funding

  • Government Support - Non-U.S.