QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 24, 2004, 24(12):3104-3114; doi:10.1523/JNEUROSCI.4444-03.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (30) Citing Articles via Google Scholar Google Scholar Articles by Li, S. Articles by Xiang, M. Search for Related Content PubMed PubMed Citation Articles by Li, S. Articles by Xiang, M.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Barhl1 Regulates Migration and Survival of Cerebellar Granule Cells by Controlling Expression of the Neurotrophin-3 Gene

Shengguo Li,¹ Feng Qiu,¹ Anlong Xu,² Sandy M. Price,¹ and Mengqing Xiang¹

¹Center for Advanced Biotechnology and Medicine and Department of Pediatrics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and ²Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China

The neurons generated at the germinal rhombic lip undergo long distance migration along divergent pathways to settle in widely dispersed locations within the hindbrain, giving rise to cerebellar granule cells and precerebellar nuclei. Neurotrophin-3 (NT-3) signaling has been shown to be required for proper migration and survival of cerebellar granule cells. The molecular bases that govern NT-3 expression within the cerebellum, however, remain unknown at present. Here we report that, during early mouse neurogenesis, the Barhl1 homeobox gene is highly expressed by the rhombic lip and rhombic lip-derived migratory neurons. Its expression is later restricted to cerebellar granule cells and precerebellar neurons extending mossy fibers, two groups of neurons that synaptically connect in the adult cerebellar system. Loss of Barhl1 function causes cerebellar phenotypes with a striking similarity to those of NT-3 conditional null mice, which include attenuated cerebellar foliation as well as defective radial migration and increased apoptotic death of granule cells. Correlating with these defects, we find that NT-3 expression is dramatically downregulated in granule cells of the posterior lobe of Barhl1^–/– cerebella. Moreover, in the precerebellar system of Barhl1^–/– mice, all five nuclei that project mossy fibers fail to form correctly because of aberrant neuronal migration and elevated apoptosis. These results suggest that Barhl1 plays an essential role in the migration and survival of cerebellar granule cells and precerebellar neurons and functionally link Barhl1 to the NT-3 signaling pathway during cerebellar development.

Key words: Barhl1; homeobox gene; neurotrophin-3; cerebellum; neuronal migration; apoptosis; rhombic lip; pontine gray nucleus

---

Received Sep 30, 2003; revised January 21, 2004; accepted February 13, 2004.

This article has been cited by other articles:

				T. Di Meglio, K. T. Nguyen-Ba-Charvet, M. Tessier-Lavigne, C. Sotelo, and A. Chedotal Molecular Mechanisms Controlling Midline Crossing by Precerebellar Neurons J. Neurosci., June 18, 2008; 28(25): 6285 - 6294. [Abstract] [Full Text] [PDF]

				F. Qiu, H. Jiang, and M. Xiang A Comprehensive Negative Regulatory Program Controlled by Brn3b to Ensure Ganglion Cell Specification from Multipotential Retinal Precursors J. Neurosci., March 26, 2008; 28(13): 3392 - 3403. [Abstract] [Full Text] [PDF]

				R. Chellappa, S. Li, S. Pauley, I. Jahan, K. Jin, and M. Xiang Barhl1 Regulatory Sequences Required for Cell-Specific Gene Expression and Autoregulation in the Inner Ear and Central Nervous System Mol. Cell. Biol., March 15, 2008; 28(6): 1905 - 1914. [Abstract] [Full Text] [PDF]

				T. Koontz, M. Bralic, J. Tomac, E. Pernjak-Pugel, G. Bantug, S. Jonjic, and W. J. Britt Altered development of the brain after focal herpesvirus infection of the central nervous system J. Exp. Med., February 18, 2008; 205(2): 423 - 435. [Abstract] [Full Text] [PDF]

				H. T. Schwartz and H. R. Horvitz The C. elegans protein CEH-30 protects male-specific neurons from apoptosis independently of the Bcl-2 homolog CED-9 Genes & Dev., December 1, 2007; 21(23): 3181 - 3194. [Abstract] [Full Text] [PDF]

				M. Yamada, M. Terao, T. Terashima, T. Fujiyama, Y. Kawaguchi, Y.-i. Nabeshima, and M. Hoshino Origin of Climbing Fiber Neurons and Their Developmental Dependence on Ptf1a J. Neurosci., October 10, 2007; 27(41): 10924 - 10934. [Abstract] [Full Text] [PDF]

				N. L. Hunter and S. M. Dymecki Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus Development, October 1, 2007; 134(19): 3449 - 3460. [Abstract] [Full Text] [PDF]

				W. Wang, D. Mullikin-Kilpatrick, J. E. Crandall, R. M. Gronostajski, E. D. Litwack, and D. L. Kilpatrick Nuclear Factor I Coordinates Multiple Phases of Cerebellar Granule Cell Development via Regulation of Cell Adhesion Molecules J. Neurosci., June 6, 2007; 27(23): 6115 - 6127. [Abstract] [Full Text] [PDF]

				R. H. Friedel, G. Kerjan, H. Rayburn, U. Schuller, C. Sotelo, M. Tessier-Lavigne, and A. Chedotal Plexin-B2 Controls the Development of Cerebellar Granule Cells J. Neurosci., April 4, 2007; 27(14): 3921 - 3932. [Abstract] [Full Text] [PDF]

				Y. Fujitani, S. Fujitani, H. Luo, F. Qiu, J. Burlison, Q. Long, Y. Kawaguchi, H. Edlund, R. J. MacDonald, T. Furukawa, et al. Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development, November 1, 2006; 133(22): 4439 - 4450. [Abstract] [Full Text] [PDF]

				D. Kawauchi, H. Taniguchi, H. Watanabe, T. Saito, and F. Murakami Direct visualization of nucleogenesis by precerebellar neurons: involvement of ventricle-directed, radial fibre-associated migration. Development, March 1, 2006; 133(6): 1113 - 1123. [Abstract] [Full Text] [PDF]

				S. Li, K. Misra, M. P. Matise, and M. Xiang Foxn4 acts synergistically with Mash1 to specify subtype identity of V2 interneurons in the spinal cord PNAS, July 26, 2005; 102(30): 10688 - 10693. [Abstract] [Full Text] [PDF]

				C. Yu, M. Dong, X. Wu, S. Li, S. Huang, J. Su, J. Wei, Y. Shen, C. Mou, X. Xie, et al. Genes "Waiting" for Recruitment by the Adaptive Immune System: The Insights from Amphioxus J. Immunol., March 15, 2005; 174(6): 3493 - 3500. [Abstract] [Full Text] [PDF]

				G. Steele-Perkins, C. Plachez, K. G. Butz, G. Yang, C. J. Bachurski, S. L. Kinsman, E. D. Litwack, L. J. Richards, and R. M. Gronostajski The Transcription Factor Gene Nfib Is Essential for both Lung Maturation and Brain Development Mol. Cell. Biol., January 15, 2005; 25(2): 685 - 698. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help