A critical role for sFRP proteins in maintaining caudal neural tube closure in mice via inhibition of BMP signaling.
Both the BMP and Wnt pathways have been implicated in directing aspects of dorsal neural tube closure and cell fate specification. However, the mechanisms that control the diverse responses to these signals are poorly understood. In this study, we provide genetic and functional evidence that the secreted sFRP1 and sFRP2 proteins, which have been primarily implicated as negative regulators of Wnt signaling, can also antagonize BMP signaling in the caudal neural tube and that this function is critical to maintain proper neural tube closure and dorsal cell fate segregation. Our studies thus reveal a novel role for specific sFRP proteins in balancing the response of cells to two critical extracellular signaling pathways.
Department of Neuroscience & Cell Biology, Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA. misrakp@umdnj.edu
Kamana
K
Misra
Michael P
MP
Matise
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D009432:Neural Crest / Q000196:embryology; D054259:Neural Tube / Q000196:embryology*; D009436:Neural Tube Defects / Q000196:embryology; D011247:Pregnancy; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology; D051153:Wnt Proteins / Q000502:physiology; D000094742:Secreted Frizzled-Related Proteins
D019485:Bone Morphogenetic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051153:Wnt Proteins; C485539:Sfrp1 protein, mouse; D000094742:Secreted Frizzled-Related Proteins; C491628:Sfrp2 protein, mouse