MGARP Regulates Mouse Neocortical Development Via Mitochondrial Positioning

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2013 Dec 11

PMID 24323429

Citations 9

Authors

Liyun Jia

Tong Liang

Xiaoyan Yu

Chao Ma

Shuping Zhang

Affiliations

Soon will be listed here.

Abstract

Neocortical development is an extremely complicated process that critically depends on the proper migration, distribution, and positioning of neural cells. Here, we identified mitochondria-localized glutamic acid-rich protein (MGARP) as a negative regulator of neocortical development. In the developing neocortex, the overexpression of MGARP by in utero electroporation impedes the radial migration of neocortical cells to their final destination. These neocortical cells failed to be normally polarized, leading to shortened axons and compromised axonal bundles. The number of dendrites was also attenuated in cells with MGARP overexpression and was expanded in MGARP-knockdown or knockout cells. Mechanistic studies indicated that overexpression of MGARP caused alterations in the structural integrity, subcellular distribution, and motility of mitochondria. The mitochondria in MGARP-overexpressing cells became "fatty" with a round morphology, and the total number of mitochondria in MGARP-overexpressing cells was also decreased in the cell body and dendrites as well as in the axons. Time lapse studies showed that the ratio of motile mitochondria was remarkably decreased in the axons of MGARP-overexpressing cells. Together, our findings suggest that MGARP negatively mediates neocortical development by regulating mitochondrial distribution and motility in neocortical neurons.

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References

Zhou M, Wang Y, Qi S, Wang J, Zhang S . The expression of a mitochondria-localized glutamic acid-rich protein (MGARP/OSAP) is under the regulation of the HPG axis. Endocrinology. 2011; 152(6):2311-20. DOI: 10.1210/en.2011-0050. View

Golan M, Mane R, Molczadzki G, Zuckerman M, Kaplan-Louson V, Huleihel M . Impaired migration signaling in the hippocampus following prenatal hypoxia. Neuropharmacology. 2009; 57(5-6):511-22. DOI: 10.1016/j.neuropharm.2009.07.028. View

Brown G, Spencer K . Steroid hormones, stress and the adolescent brain: a comparative perspective. Neuroscience. 2012; 249:115-28. DOI: 10.1016/j.neuroscience.2012.12.016. View

Mochida G . Genetics and biology of microcephaly and lissencephaly. Semin Pediatr Neurol. 2009; 16(3):120-6. PMC: 3565221. DOI: 10.1016/j.spen.2009.07.001. View

Lapray D, Popova I, Kindler J, Jorquera I, Becq H, Manent J . Spontaneous epileptic manifestations in a DCX knockdown model of human double cortex. Cereb Cortex. 2010; 20(11):2694-701. DOI: 10.1093/cercor/bhq014. View

Chen H, Chan D . Mitochondrial dynamics--fusion, fission, movement, and mitophagy--in neurodegenerative diseases. Hum Mol Genet. 2009; 18(R2):R169-76. PMC: 2758711. DOI: 10.1093/hmg/ddp326. View

Behl C . Oestrogen as a neuroprotective hormone. Nat Rev Neurosci. 2002; 3(6):433-42. DOI: 10.1038/nrn846. View

Brookes P, Yoon Y, Robotham J, Anders M, Sheu S . Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am J Physiol Cell Physiol. 2004; 287(4):C817-33. DOI: 10.1152/ajpcell.00139.2004. View

van Spronsen M, Mikhaylova M, Lipka J, Schlager M, van den Heuvel D, Kuijpers M . TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites. Neuron. 2013; 77(3):485-502. DOI: 10.1016/j.neuron.2012.11.027. View

10.

Li Y, Lim S, Hoffman D, Aspenstrom P, Federoff H, Rempe D . HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters mitochondrial distribution and transport. J Cell Biol. 2009; 185(6):1065-81. PMC: 2711615. DOI: 10.1083/jcb.200811033. View

11.

Cuezva J, Ostronoff L, Ricart J, Lopez de Heredia M, Di Liegro C, Izquierdo J . Mitochondrial biogenesis in the liver during development and oncogenesis. J Bioenerg Biomembr. 1997; 29(4):365-77. DOI: 10.1023/a:1022450831360. View

12.

Pang T, Atefy R, Sheen V . Malformations of cortical development. Neurologist. 2008; 14(3):181-91. PMC: 3547618. DOI: 10.1097/NRL.0b013e31816606b9. View

13.

Lopez-Bendito G, Cautinat A, Sanchez J, Bielle F, Flames N, Garratt A . Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in thalamocortical axon navigation. Cell. 2006; 125(1):127-42. PMC: 2365888. DOI: 10.1016/j.cell.2006.01.042. View

14.

Loy R, Milner T . Sexual dimorphism in extent of axonal sprouting in rat hippocampus. Science. 1980; 208(4449):1282-4. DOI: 10.1126/science.7375941. View

15.

Saito T, Nakatsuji N . Efficient gene transfer into the embryonic mouse brain using in vivo electroporation. Dev Biol. 2002; 240(1):237-46. DOI: 10.1006/dbio.2001.0439. View

16.

Gomes L, Scorrano L . Mitochondrial morphology in mitophagy and macroautophagy. Biochim Biophys Acta. 2012; 1833(1):205-12. DOI: 10.1016/j.bbamcr.2012.02.012. View

17.

Squier W, Jansen A . Abnormal development of the human cerebral cortex. J Anat. 2010; 217(4):312-23. PMC: 2992410. DOI: 10.1111/j.1469-7580.2010.01288.x. View

18.

Kang J, Tian J, Pan P, Zald P, Li C, Deng C . Docking of axonal mitochondria by syntaphilin controls their mobility and affects short-term facilitation. Cell. 2008; 132(1):137-48. PMC: 2259239. DOI: 10.1016/j.cell.2007.11.024. View

19.

Bailey M, Coon S, Carter D, Humphries A, Kim J, Shi Q . Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling. J Biol Chem. 2008; 284(12):7606-22. PMC: 2658055. DOI: 10.1074/jbc.M808394200. View

20.

Crino P . Focal brain malformations: seizures, signaling, sequencing. Epilepsia. 2009; 50 Suppl 9:3-8. DOI: 10.1111/j.1528-1167.2009.02289.x. View