ZFIN ID: ZDB-PUB-190409-5
Morphogenesis and axis specification occur in parallel during optic cup and optic fissure formation, differentially modulated by BMP and Wnt
Eckert, P., Knickmeyer, M.D., Schütz, L., Wittbrodt, J., Heermann, S.
Date: 2019
Source: Open Biology   9: 180179 (Journal)
Registered Authors: Heermann, Stephan
Keywords: BMP, Wnt, coloboma, morphogenesis, optic cup, optic fissure
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism
  • Coloboma/embryology
  • Coloboma/genetics
  • Coloboma/metabolism
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • In Situ Hybridization/methods
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Microscopy, Confocal
  • Morphogenesis*
  • Optic Disk/embryology
  • Optic Disk/metabolism*
  • Time-Lapse Imaging/methods
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 30958096 Full text @ Open Biol.
Optic cup morphogenesis is an intricate process. Especially, the formation of the optic fissure is not well understood. Persisting optic fissures, termed coloboma, are frequent causes for congenital blindness. Even though the defective fusion of the fissure margins is the most acknowledged reason for coloboma, highly variable morphologies of coloboma phenotypes argue for a diverse set of underlying pathomechanisms. Here, we investigate optic fissure morphogenesis in zebrafish to identify potential morphogenetic defects resulting in coloboma. We show that the formation of the optic fissure depends on tissue flow movements, integrated into the bilateral distal epithelial flow forming the optic cup. On the temporal side, the distal flow translates into a ventral perpendicular flow, shaping the temporal fissure margin. On the nasal side, however, the distal flow is complemented by tissue derived from the optic stalk, shaping the nasal fissure margin. Notably, a distinct population of TGFβ-signalling positive cells is translocated from the optic stalk into both fissure margins. Furthermore, we show that induced BMP signalling as well as Wnt-signalling inhibition result in morphogenetic defects of the optic fissure. Our data also indicate that morphogenesis is crucial for a proper positioning of pre-specified dorsal-ventral optic cup domains.