title: Direct Interactions Between Gli3, Wnt8b, and Fgfs Underlie Patterning of the Dorsal Telencephalon.
abstract: A key step in the development of the cerebral cortex is a patterning process, which subdivides the telencephalon into several molecularly distinct domains and is critical for cortical arealization. This process is dependent on a complex network of interactions between signaling molecules of the Fgf and Wnt gene families and the Gli3 transcription factor gene, but a better knowledge of the molecular basis of the interplay between these factors is required to gain a deeper understanding of the genetic circuitry underlying telencephalic patterning. Using DNA-binding and reporter gene assays, we here investigate the possibility that Gli3 and these signaling molecules interact by directly regulating each other's expression. We show that Fgf signaling is required for Wnt8b enhancer activity in the cortical hem, whereas Wnt/β-catenin signaling represses Fgf17 forebrain enhancer activity. In contrast, Fgf and Wnt/β-catenin signaling cooperate to regulate Gli3 expression. Taken together, these findings indicate that mutual interactions between Gli3, Wnt8b, and Fgf17 are crucial elements of the balance between these factors thereby conferring robustness to the patterning process. Hence, our study provides a framework for understanding the genetic circuitry underlying telencephalic patterning and how defects in this process can affect the formation of cortical areas.
authors.affiliation: Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, EdinburghEH8 9XD, UK.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hasenpusch-Theil
authors.affiliation: Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, EdinburghEH8 9XD, UK.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Watson
authors.affiliation: Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, EdinburghEH8 9XD, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Theil
mesh_terms: D000818:Animals; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D016548:Prosencephalon / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D013788:Thalamus / Q000196:embryology / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology; D000074290:Zinc Finger Protein Gli3 / Q000235:genetics / Q000502:physiology*
chemical_list: C484726:Fgf17 protein, mouse; C465571:Gli3 protein, mouse; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins; C490603:Wnt8b protein, mouse; D000074290:Zinc Finger Protein Gli3; D005346:Fibroblast Growth Factors
keywords: Fgf15; Fgf17; Gli3; Wnt8b; patterning