Failure to express GAP-43 leads to disruption of a multipotent precursor and inhibits astrocyte differentiation

Molecular and Cellular Neurosciences
Yiping ShenKarina F Meiri

Abstract

The nervous system-specific protein GAP-43 is significantly upregulated in neurons and glia that are differentiating. In P19 EC cells that do not express GAP-43, neurogenesis is inhibited; many immature neurons apoptose and the survivors do not mature morphologically. Here we show that the initial defect is in an early precursor with characteristics of a neural stem cell, which failed to respond normally to retinoic acid (RA). As a consequence, its progeny had altered cell fates: In addition to the neuronal defects previously reported, RC1-labeled radial glia failed to exit the cell cycle, accumulated, and failed to acquire GFAP immunoreactivity. However, leukemia inhibitory factor (LIF) could stimulate GFAP expression suggesting that astrocytes not derived from radial glia are less affected by absence of GAP-43. Differentiation of radial glia-derived astrocytes was also inhibited in glial cultures from GAP-43 (-/-) cerebellum, and in GAP-43 (-/-) telencephalon in vivo, differentiation of astrocytes derived from both radial and nonradial glia lineages were both affected: In the glial wedge, GFAP-labeled radial glia-derived astrocytes were reduced consistent with the interpretation that they may be unable to deflect GAP-43 (-/-)...Continue Reading

References

Oct 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·G S EisenbarthM Nirenberg
Jul 1, 1990·The Journal of Cell Biology·A da Cunha, L Vitković
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·L VitkovićM Mersel
Jan 1, 1982·Journal of Neuroscience Research·A Michler-Stuke, J E Bottenstein
Mar 1, 1984·Developmental Biology·P BovolentaC A Mason
Aug 1, 1982·The Journal of Cell Biology·E M Jones-VilleneuveV I Kalnins
Aug 1, 1995·Neuropathology and Applied Neurobiology·G MorettoS U Kim
Feb 26, 1993·Biochemical and Biophysical Research Communications·S M BloemersS W de Laat
May 1, 1996·Brain Research. Molecular Brain Research·S KanazirL Rakic
Aug 1, 1997·Developmental Biology·M S Rao, M Mayer-Proschel
Nov 14, 1997·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M SensenbrennerJ C Deloulme
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·D L MaierK F Meiri
Aug 14, 1999·The Journal of Biological Chemistry·C EliassonM Pekny
Sep 16, 1999·FEBS Letters·K NakashimaT Taga
Mar 15, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·E BoutouR Matsas
Mar 17, 2000·Glia·J C LeeM S Rao
Jul 19, 2000·Journal of Neurochemistry·L RiboniG Tettamanti
Apr 3, 2001·Annual Review of Neuroscience·G Lemke
Apr 3, 2001·Nature Reviews. Neuroscience·A Alvarez-BuyllaA D Tramontin

❮ Previous
Next ❯

Citations

Feb 22, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·Emil TrofimiukJan J Braszko
Feb 8, 2008·Molecular Biology of the Cell·Anneke E SchwobKarina F Meiri
Feb 28, 2015·Archives of Biochemistry and Biophysics·Karina De MolinerAna M Adamo
Aug 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jia-Ling TeoMichael Kahn
Feb 25, 2011·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Junpeng ZhaoQunyuan Xu
Sep 26, 2009·Seminars in Pediatric Neurology·Amber-Lee S Donahoo, Linda J Richards
Jul 11, 2009·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Junpeng ZhaoQunyuan Xu
Feb 6, 2007·Current Opinion in Neurobiology·Charlotta LindwallLinda J Richards
Nov 29, 2007·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·M SlevinJ Gaffney
Feb 13, 2013·Journal of Biomedical Materials Research. Part a·Marie Hronik-TupajDavid L Kaplan
Jul 22, 2018·In Vitro Cellular & Developmental Biology. Animal·Isha Verma, Polani B Seshagiri

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Fate Specification

Cell fate specification is determined by complex signal transduction pathways including Notch and the Sonic hedgehog signaling pathway. Here is the latest research on regulation of cell fate determination.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Astrocytes in Repair & Regeneration

Astrocytes are glial cells found within the CNS and are able to regenerate new neurons. They become activated during CNS injury and disease. The activation leads to the transcription of new genes and the repair and regeneration of neurons. Discover the latest research on astrocytes in repair and regeneration here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis