title: Krüppel-Like Factor 4 (KLF4) Is Not Required for Retinal Cell Differentiation.
abstract: During early vertebrate eye development, a regulatory network of transcription factors regulates retinal cell differentiation and survival into adulthood. Among those factors, Krüppel-like factor 4 (KLF4) plays the dual role of maintaining the stem cell status of retinal progenitors cells and repressing the intrinsic axon regeneration ability in retinal ganglion cells (RGCs) after injury. This study further investigated whether KLF4 plays a role in early retinal cell differentiation or survival into adulthood. We examined different types of retinal neurons, including RGCs, amacrine cells, bipolar cells, Müller cells, and photoreceptor cells, in adult mice in which KLF4 was conditionally deleted in early retinal development using Chx10-promoted Cre by immunohistochemistry. We compared the numbers of retinal neurons and the thickness of photoreceptor and nerve fiber layers between Chx10-Cre-driven KLF4 deletion mice and wild-type mice. There was no significant difference in cell number among any of the retinal cell types or in photoreceptor layer thickness with KLF4 deletion during early development. The thickness of axon bundles in the nerve fiber layer in the Chx10 conditional KLF4 knock-out mice was greater than that in wild-type mice. These results suggest that KLF4 is not required for retinal cell differentiation or survival, but does normally limit retinal ganglion cell axon bundle thickness. These data support a hypothesis that KLF4 suppresses axon growth during development.
authors.affiliation: Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, California 92093; Department of Ophthalmology, Changsha First People's Hospital, Changsha 410008, Hunan, China.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Ophthalmology and Shiley Eye Institute, University of California San Diego , La Jolla, California 92093.
authors.forename: Peter X
authors.identifier: 0000-0001-7392-6224
authors.initials: PX
authors.lastname: Shaw
authors.affiliation: Department of Ophthalmology and Shiley Eye Institute, University of California San Diego , La Jolla, California 92093.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, California 92093; Byers Eye Institute at Stanford, Palo Alto, California 94303.
authors.forename: Jeffrey L
authors.identifier: 0000-0002-1390-7360
authors.initials: JL
authors.lastname: Goldberg
mesh_terms: D025042:Amacrine Cells / Q000166:cytology / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D063928:Ependymoglial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000502:physiology; D012160:Retina / Q000166:cytology* / Q000254:growth & development*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology; D055351:Retinal Neurons / Q000166:cytology* / Q000502:physiology*
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors
keywords: Krüppel-like factor 4; axon growth; retinal development; retinal ganglion cells