title: Lamin B1 and lamin B2 are long-lived proteins with distinct functions in retinal development.
abstract: Lamin B1 and lamin B2 are essential building blocks of the nuclear lamina, a filamentous meshwork lining the nucleoplasmic side of the inner nuclear membrane. Deficiencies in lamin B1 and lamin B2 impair neurodevelopment, but distinct functions for the two proteins in the development and homeostasis of the CNS have been elusive. Here we show that embryonic depletion of lamin B1 in retinal progenitors and postmitotic neurons affects nuclear integrity, leads to the collapse of the laminB2 meshwork, impairs neuronal survival, and markedly reduces the cellularity of adult retinas. In stark contrast, a deficiency of lamin B2 in the embryonic retina has no obvious effect on lamin B1 localization or nuclear integrity in embryonic retinas, suggesting that lamin B1, but not lamin B2, is strictly required for nucleokinesis during embryonic neurogenesis. However, the absence of lamin B2 prevents proper lamination of adult retinal neurons, impairs synaptogenesis, and reduces cone photoreceptor survival. We also show that lamin B1 and lamin B2 are extremely long-lived proteins in rod and cone photoreceptors. OF interest, a complete absence of both proteins during postnatal life has little or no effect on the survival and function of cone photoreceptors.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: David
authors.initials: D
authors.lastname: Razafsky
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Candace
authors.initials: C
authors.lastname: Ward
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Chloe
authors.initials: C
authors.lastname: Potter
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Yunlu
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Kefalov
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.affiliation: Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095 Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110 hodzicd@vision.wustl.edu.
authors.forename: Didier
authors.initials: D
authors.lastname: Hodzic
mesh_terms: D000818:Animals; D034921:Lamin Type B / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D034881:Nuclear Lamina / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000378:metabolism / Q000502:physiology
chemical_list: D034921:Lamin Type B