Optic vesicle morphogenesis requires primary cilia

Luciano Fiore; Nozomu Takata; Sandra Acosta; Wanshu Ma; Tanushree Pandit; Michael Oxendine; Guillermo Oliver

doi:10.1016/j.ydbio.2020.02.016

Optic vesicle morphogenesis requires primary cilia

Dev Biol. 2020 Jun 15;462(2):119-128. doi: 10.1016/j.ydbio.2020.02.016. Epub 2020 Mar 10.

Authors

Luciano Fiore¹, Nozomu Takata¹, Sandra Acosta², Wanshu Ma¹, Tanushree Pandit³, Michael Oxendine¹, Guillermo Oliver⁴

Affiliations

¹ Center for Vascular and Developmental Biology, Feinberg Cardiovascular and Renal Research Institute (FCVRRI), Northwestern University, Chicago, IL, USA.
² Center for Vascular and Developmental Biology, Feinberg Cardiovascular and Renal Research Institute (FCVRRI), Northwestern University, Chicago, IL, USA; Institute of Evolutive Biology, Pompeu Fabra University, Barcelona, Spain.
³ Department of Genetics, St. Jude Children's Research Hospital, Memphis, TN, USA.
⁴ Center for Vascular and Developmental Biology, Feinberg Cardiovascular and Renal Research Institute (FCVRRI), Northwestern University, Chicago, IL, USA. Electronic address: [email protected].

Abstract

Arl13b is a gene known to regulate ciliogenesis. Functional alterations in this gene's activity have been associated with Joubert syndrome. We found that in Arl13 null mouse embryos the orientation of the optic cup is inverted, such that the lens is abnormally surrounded by an inverted optic cup whose retina pigmented epithelium is oddly facing the surface ectoderm. Loss of Arl13b leads to the disruption of optic vesicle's patterning and expansion of ventral fates. We show that this phenotype is consequence of miss-regulation of Sonic hedgehog (Shh) signaling and demonstrate that the Arl13b^-/- eye phenotype can be rescued by deletion of Gli2, a downstream effector of the Shh pathway. This work identified an unexpected role of primary cilia during the morphogenetic movements required for the formation of the eye.

Keywords: Arl13b; Eye; Morphogenesis; Mouse; Optic vesicle; Primary cilia; Shh.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

ADP-Ribosylation Factors / genetics
ADP-Ribosylation Factors / metabolism*
Animals
Body Patterning / genetics
Bone Morphogenetic Protein 4 / metabolism
Cilia / genetics
Cilia / metabolism*
Embryonic Development
Eye / embryology*
Eye / metabolism
Eye Proteins / genetics
Eye Proteins / metabolism
Gene Expression Regulation, Developmental / genetics
Hedgehog Proteins / metabolism
Homeobox Protein SIX3
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Humans
Lens, Crystalline / embryology
Lens, Crystalline / metabolism
Male
Mice
Mice, Knockout
Morphogenesis
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism
Organogenesis
Retinal Pigment Epithelium / embryology
Retinal Pigment Epithelium / metabolism
Signal Transduction / genetics
Wnt1 Protein / genetics
Wnt1 Protein / metabolism
Zinc Finger Protein Gli2 / genetics
Zinc Finger Protein Gli2 / metabolism

Substances

Arl13b protein, mouse
Bone Morphogenetic Protein 4
Eye Proteins
Gli2 protein, mouse
Hedgehog Proteins
Homeodomain Proteins
Nerve Tissue Proteins
Wnt1 Protein
Wnt1 protein, mouse
Zinc Finger Protein Gli2
ADP-Ribosylation Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding