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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 15, 2003, 23(12):5178-5186

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 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 Web of Science (66) Citing Articles via Google Scholar Google Scholar Articles by Farkas, L. M. Articles by Krieglstein, K. Search for Related Content PubMed PubMed Citation Articles by Farkas, L. M. Articles by Krieglstein, K.

 Previous Article  |  Next Article 

Transforming Growth Factor-s Are Essential for the Development of Midbrain Dopaminergic Neurons In Vitro and In Vivo

Lilla M. Farkas,^1 * Nicole Dünker,^2 * Eleni Roussa,² Klaus Unsicker,¹ and Kerstin Krieglstein^1,2

¹Neuroanatomy, Interdisciplinary Center for Neurosciences, University of Heidelberg, D-69120 Heidelberg, Germany, and ²Center of Anatomy, University of Göttingen, 37075 Göttingen, Germany

Development of midbrain dopaminergic neurons is known to depend on inductive signals derived from the ventral midline, including Sonic hedgehog (Shh) as one of the identified molecules. Here we show that in addition to Shh, transforming growth factor (TGF)- is required for both induction and survival of ventrally located midbrain dopaminergic neurons. Like Shh, TGF- is expressed in early embryonic structures such as notochord and floor plate, as well as in the area where mibrain dopaminergic neurons are developing. Treatment of cells dissociated from the rat embryonic day (E) 12 mibrain floor with TGF- significantly increases the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons within 24 hr. Neutralization of TGF- in vitro completely abolishes the induction of dopaminergic neurons. In the absence of TGF-, Shh cannot induce TH-positive neurons, and vice versa, neutralizing endogenous Shh abolishes the capacity of TGF- to induce dopaminergic neurons in vitro. Furthermore, neutralization of TGF- in vivo during chick E2–7 but not E4–7 resulted in a significant reduction in TH-positive neurons in the ventral midbrain floor but not in the locus coeruleus or diencephalon, which suggests that the TGF- is required for the induction of mesencephalic dopaminergic neurons with a critical time period at E2/E3. Furthermore, neutralization of TGF- between E6 and 10, a time period during maturation of mesencephalic dopaminergic neurons when no further inductive cues are required, also resulted in a significant loss of dopaminergic neurons, suggesting that TGF- is required for the promotion of survival of ventral midbrain dopaminergic neurons as well. Together, our results identify TGF- as an essential mediator for the induction and maintenance of midbrain dopaminergic neurons.

Key words: TGF-; BMP; dopaminergic neurons; Sonic hedgehog; midline; floor plate; phenotype induction

---

Received Sep. 25, 2002; revised Apr. 4, 2003; accepted Apr. 8, 2003.

This article has been cited by other articles:

				T. Vogel, S. Ahrens, N. Buttner, and K. Krieglstein Transforming Growth Factor {beta} Promotes Neuronal Cell Fate of Mouse Cortical and Hippocampal Progenitors In Vitro and In Vivo: Identification of Nedd9 as an Essential Signaling Component Cereb Cortex, July 8, 2009; (2009) bhp134v1. [Abstract] [Full Text] [PDF]

				J. Saarimaki-Vire, P. Peltopuro, L. Lahti, T. Naserke, A. A. Blak, D. M. Vogt Weisenhorn, K. Yu, D. M. Ornitz, W. Wurst, and J. Partanen Fibroblast Growth Factor Receptors Cooperate to Regulate Neural Progenitor Properties in the Developing Midbrain and Hindbrain J. Neurosci., August 8, 2007; 27(32): 8581 - 8592. [Abstract] [Full Text] [PDF]

				W. Zhang, E.-J. Shin, T. Wang, P. H. Lee, H. Pang, M.-B. Wie, W.-K. Kim, S.-J. Kim, W.-H. Huang, Y. Wang, et al. 3-Hydroxymorphinan, a metabolite of dextromethorphan, protects nigrostriatal pathway against MPTP-elicited damage both in vivo and in vitro FASEB J, December 1, 2006; 20(14): 2496 - 2511. [Abstract] [Full Text] [PDF]

				S.-L. Ang Transcriptional control of midbrain dopaminergic neuron development Development, September 15, 2006; 133(18): 3499 - 3506. [Abstract] [Full Text] [PDF]

				F. M. J. Jacobs, S. M. Smits, K. J. M. Hornman, J. P. H. Burbach, and M. P. Smidt Strategies to unravel molecular codes essential for the development of meso-diencephalic dopaminergic neurons J. Physiol., September 1, 2006; 575(2): 397 - 402. [Abstract] [Full Text] [PDF]

				N. Prakash and W. Wurst Genetic networks controlling the development of midbrain dopaminergic neurons J. Physiol., September 1, 2006; 575(2): 403 - 410. [Abstract] [Full Text] [PDF]

				M. S. Buckwalter, M. Yamane, B. S. Coleman, B. K. Ormerod, J. T. Chin, T. Palmer, and T. Wyss-Coray Chronically Increased Transforming Growth Factor-{beta}1 Strongly Inhibits Hippocampal Neurogenesis in Aged Mice Am. J. Pathol., July 1, 2006; 169(1): 154 - 164. [Abstract] [Full Text] [PDF]

				N. Prakash, C. Brodski, T. Naserke, E. Puelles, R. Gogoi, A. Hall, M. Panhuysen, D. Echevarria, L. Sussel, D. M. V. Weisenhorn, et al. A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo Development, January 1, 2006; 133(1): 89 - 98. [Abstract] [Full Text] [PDF]

				S. Fuke, N. Sasagawa, and S. Ishiura Identification and Characterization of the Hesr1/Hey1 as a Candidate trans-Acting Factor on Gene Expression through the 3' Non-Coding Polymorphic Region of the Human Dopamine Transporter (DAT1) Gene J. Biochem., February 1, 2005; 137(2): 205 - 216. [Abstract] [Full Text] [PDF]

				A. L. Perrier, V. Tabar, T. Barberi, M. E. Rubio, J. Bruses, N. Topf, N. L. Harrison, and L. Studer From the Cover: Derivation of midbrain dopamine neurons from human embryonic stem cells PNAS, August 24, 2004; 101(34): 12543 - 12548. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help