title: Sprouty1 and Sprouty2 limit both the size of the otic placode and hindbrain Wnt8a by antagonizing FGF signaling.
abstract: Multiple signaling molecules, including Fibroblast Growth Factor (FGF) and Wnt, induce two patches of ectoderm on either side of the hindbrain to form the progenitor cell population for the inner ear, or otic placode. Here we report that in Spry1, Spry2 compound mutant embryos (Spry1⁻/⁻; Spry2⁻/⁻ embryos), the otic placode is increased in size. We demonstrate that the otic placode is larger due to the recruitment of cells, normally destined to become cranial epidermis, into the otic domain. The enlargement of the otic placode observed in Spry1⁻/⁻; Spry2⁻/⁻ embryos is preceded by an expansion of a Wnt8a expression domain in the adjacent hindbrain. We demonstrate that both the enlargement of the otic placode and the expansion of the Wnt8a expression domain can be rescued in Spry1⁻/⁻; Spry2⁻/⁻ embryos by reducing the gene dosage of Fgf10. Our results define a FGF-responsive window during which cells can be continually recruited into the otic domain and uncover SPRY regulation of the size of a putative Wnt inductive center.
authors.affiliation: Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Mahoney Rogers
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Katherine
authors.initials: K
authors.lastname: Shim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D004475:Ectoderm / Q000473:pathology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008938:Mitosis; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D010750:Phosphoproteins / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D012249:Rhombencephalon / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D010750:Phosphoproteins; C425468:Spry1 protein, mouse; D051153:Wnt Proteins; C507016:Wnt8a protein, mouse; D005346:Fibroblast Growth Factors; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse