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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 16, 2008, 28(3):622-632; doi:10.1523/JNEUROSCI.2986-07.2008

This Article Full Text Full Text (PDF) Supplemental Data 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 Google Scholar Articles by Arlotta, P. Articles by Macklis, J. D. PubMed PubMed Citation Articles by Arlotta, P. Articles by Macklis, J. D.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Ctip2 Controls the Differentiation of Medium Spiny Neurons and the Establishment of the Cellular Architecture of the Striatum

Paola Arlotta,^1 * Bradley J. Molyneaux,^1 * Denis Jabaudon,¹ Yutaka Yoshida,² and Jeffrey D. Macklis¹

¹Massachusetts General Hospital–Harvard Medical School Center for Nervous System Repair, Nayef Al-Rodhan Laboratories, Departments of Neurosurgery and Neurology, Program in Neuroscience, and Harvard Stem Cell Institute, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, and ²Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Howard Hughes Medical Institute, Columbia University, New York, New York 10032

Correspondence should be addressed to Jeffrey D. Macklis at the above address. Email: jeffrey_macklis{at}hms.harvard.edu

Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntington's disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, although it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1 (µ-opioid receptor 1), glutamate receptor 1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2^–/– striatum, suggesting a failure by MSN to repel these cells in the absence of Ctip2. This is associated with abnormal dopaminergic innervation of the mutant striatum and dramatic changes in gene expression, including dysregulation of molecules involved in cellular repulsion. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum.

Key words: Ctip2; striatum; medium spiny neurons; striasomes; striatal patches; secretagogin

---

Received April 13, 2006; revised Oct. 7, 2007; accepted Dec. 1, 2007.

Correspondence should be addressed to Jeffrey D. Macklis at the above address. Email: jeffrey_macklis{at}hms.harvard.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help