title: Knockdown of CXCL14 disrupts neurovascular patterning during ocular development.
abstract: The C-X-C motif ligand 14 (CXCL14) is a recently discovered chemokine that is highly conserved in vertebrates and expressed in various embryonic and adult tissues. CXCL14 signaling has been implicated to function as an antiangiogenic and anticancer agent in adults. However, its function during development is unknown. We previously identified novel expression of CXCL14 mRNA in various ocular tissues during development. Here, we show that CXCL14 protein is expressed in the anterior eye at a critical time during neurovascular development and in the retina during neurogenesis. We report that RCAS-mediated knockdown of CXCL14 causes severe neural defects in the eye including precocious and excessive innervation of the cornea and iris. Absence of CXCL14 results in the malformation of the neural retina and misprojection of the retinal ganglion neurons. The ocular neural defects may be due to loss of CXCL12 modulation since recombinant CXCL14 diminishes CXCL12-induced axon growth in vitro. Furthermore, we show that knockdown of CXCL14 causes neovascularization of the cornea. Altogether, our results show for the first time that CXCL14 plays a critical role in modulating neurogenesis and inhibiting ectopic vascularization of the cornea during ocular development.
authors.affiliation: BioSciences, Rice University, 6100 Main Street, Houston, TX, United States; Universidad Santo Tomas, sede Puerto Montt, Buenavecindad #91, Décima región de los Lagos, Chile.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Ojeda
authors.affiliation: BioSciences, Rice University, 6100 Main Street, Houston, TX, United States.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Munjaal
authors.affiliation: BioSciences, Rice University, 6100 Main Street, Houston, TX, United States. Electronic address: lwigale@rice.edu.
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Lwigale
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D019743:Chemokines, CXC / Q000378:metabolism*; D002645:Chickens; D003315:Cornea / Q000294:innervation / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism; D019573:Epithelium, Corneal / Q000378:metabolism; D005123:Eye / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D007498:Iris / Q000196:embryology / Q000294:innervation; D008954:Models, Biological; D009420:Nervous System / Q000098:blood supply* / Q000196:embryology*; D011784:Quail; D034741:RNA, Small Interfering / Q000378:metabolism; D012160:Retina / Q000473:pathology; D014276:Trigeminal Nerve / Q000196:embryology / Q000378:metabolism
chemical_list: D019743:Chemokines, CXC; D034741:RNA, Small Interfering
keywords: CXCL14; Chemokine; Cornea; Neurogenesis; Ocular nerves; Vasculogenesis