title: Loss of Axin2 Causes Ocular Defects During Mouse Eye Development.
abstract: OBJECTIVE
  The scaffold protein Axin2 is an antagonist and universal target of the Wnt/β-catenin pathway. Disruption of Axin2 may lead to developmental eye defects; however, this has not been examined. The purpose of this study was to investigate the role of Axin2 during ocular and extraocular development in mouse.
  
  
  METHODS
  Animals heterozygous and homozygous for a Axin2lacZ knock-in allele were analyzed at different developmental stages for reporter expression, morphology as well as for the presence of ocular and extraocular markers using histologic and immunohistochemical techniques.
  
  
  RESULTS
  During early eye development, the Axin2lacZ reporter was expressed in the periocular mesenchyme, RPE, and optic stalk. In the developing retina, Axin2lacZ reporter expression was initiated in ganglion cells at late embryonic stages and robustly expressed in subpopulations of amacrine and horizontal cells postnatally. Activation of the Axin2lacZ reporter overlapped with labeling of POU4F1, PAX6, and Calbindin. Germline deletion of Axin2 led to variable ocular phenotypes ranging from normal to severely defective eyes exhibiting microphthalmia, coloboma, lens defects, and expanded ciliary margin. These defects were correlated with abnormal tissue patterning in individual affected tissues, such as the optic fissure margins in the ventral optic cup and in the expanded ciliary margin.
  
  
  CONCLUSIONS
  Our results reveal a critical role for Axin2 during ocular development, likely by restricting the activity of the Wnt/β-catenin pathway.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Ashley
authors.initials: A
authors.lastname: Alldredge
authors.affiliation: Department of Ophthalmology and Visual Sciences, Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fuhrmann
mesh_terms: D000483:Alleles; D000818:Animals; D060466:Axin Protein / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005123:Eye / Q000254:growth & development* / Q000378:metabolism; D005128:Eye Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D038081:Organogenesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D060449:Wnt Signaling Pathway
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse