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The Journal of Neuroscience, December 24, 2008, 28(52):14074-14087; doi:10.1523/JNEUROSCI.3188-08.2008

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Development/Plasticity/Repair
Id2 Is Required for Specification of Dopaminergic Neurons during Adult Olfactory Neurogenesis

Matthew C. Havrda,^1,2 Brent T. Harris,⁴ Akio Mantani,⁵ Nora M. Ward,^1,2 Brenton R. Paolella,^1,2 Verginia C. Cuzon,³ Hermes H. Yeh,³ and Mark A. Israel^1,2

¹Norris Cotton Cancer Center and Departments of ²Genetics and ³Physiology, Dartmouth Medical School, and ⁴Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, and ⁵Division of Psychiatry, Yoshida General Hospital, Hiroshima 731-05, Japan

Correspondence should be addressed to Dr. Matthew C. Havrda, Norris Cotton Cancer Center, Dartmouth Medical School, 1 Medical Center Drive, Rubin 7, Room 751, Lebanon, NH 03756. Email: Matthew.C.Havrda{at}Dartmouth.edu

Understanding the biology of adult neural stem cells has important implications for nervous system development and may contribute to our understanding of neurodegenerative disorders and their treatment. We have characterized the process of olfactory neurogenesis in adult mice lacking inhibitor of DNA binding 2^–/– (Id2^–/–). We found a diminished olfactory bulb containing reduced numbers of granular and periglomerular neurons with a distinct paucity of dopaminergic periglomerular neurons. While no deficiency of the stem cell compartment was detectable, migrating neuroblasts in Id2^–/– mutant mice prematurely undergo astroglial differentiation within a disorganized rostral migratory stream. Further, when evaluated in vitro loss of Id2 results in decreased proliferation of neural progenitors and decreased expression of the Hes1 and Ascl1 (Mash1) transcription factors, known mediators of neuronal differentiation. These data support a novel role for sustained Id2 expression in migrating neural progenitors mediating olfactory dopaminergic neuronal differentiation in adult animals.

Key words: Id2; dopaminergic; olfactory; adult; neurogenesis; subventricular zone

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Received July 9, 2008; revised Aug. 19, 2008; accepted Nov. 13, 2008.

Correspondence should be addressed to Dr. Matthew C. Havrda, Norris Cotton Cancer Center, Dartmouth Medical School, 1 Medical Center Drive, Rubin 7, Room 751, Lebanon, NH 03756. Email: Matthew.C.Havrda{at}Dartmouth.edu

This article has been cited by other articles:

				J. M. Murad, C. S. Place, C. Ran, S. K. N. Hekmatyar, N. P. Watson, R. A. Kauppinen, and M. A. Israel Inhibitor of DNA Binding 4 (ID4) Regulation of Adipocyte Differentiation and Adipose Tissue Formation in Mice J. Biol. Chem., July 30, 2010; 285(31): 24164 - 24173. [Abstract] [Full Text] [PDF]

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