RGD Reference Report - Effects on differentiation of embryonic ventral midbrain progenitors by Lmx1a, Msx1, Ngn2, and Pitx3. - Rat Genome Database

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Effects on differentiation of embryonic ventral midbrain progenitors by Lmx1a, Msx1, Ngn2, and Pitx3.

Authors: Roybon, L  Hjalt, T  Christophersen, NS  Li, JY  Brundin, P 
Citation: Roybon L, etal., J Neurosci. 2008 Apr 2;28(14):3644-56. doi: 10.1523/JNEUROSCI.0311-08.2008.
RGD ID: 11535083
Pubmed: PMID:18385323   (View Abstract at PubMed)
PMCID: PMC6671084   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.0311-08.2008   (Journal Full-text)

Neurons derived from neural stem cells could potentially be used for cell therapy in neurodegenerative disorders, such as Parkinson's disease. To achieve controlled differentiation of neural stem cells, we expressed transcription factors involved in the development of midbrain dopaminergic neurons in rat and human neural progenitors. Using retroviral-mediated transgene delivery, we overexpressed Lmx1a (LIM homeobox transcription factor 1, alpha), Msx1 (msh homeobox homolog 1), Ngn2 (neurogenin 2), or Pitx3 (paired-like homeodomain transcription factor 3) in neurospheres derived from embryonic day 14.5 rat ventral mesencephalic progenitors. We also expressed either Lmx1a or Msx1 in the human embryonic midbrain-derived progenitor cell line NGC-407. Rat cells transduced with Ngn2 exited the cell cycle and expressed the neuronal marker microtubule-associated protein 2 and catecholamine-neuron protein vesicular monoamine transporter 2. Interestingly, Pitx3 downregulated the expression of SOX2 (SRY-box containing gene 2) and Nestin, altered cell morphology, but never induced neuronal or glial differentiation. Ngn2 exhibited a strong neuron-inducing effect. In contrast, few Lmx1a-transduced cells matured into neurons, and Msx1 overexpression promoted oligodendrogenesis rather than neuronal differentiation. Importantly, none of these four genes, alone or in combination, enhanced differentiation of rat neural stem cells into dopaminergic neurons. Notably, the overexpression of Lmx1a, but not Msx1, in human neural progenitors increased the yield of tyrosine hydroxylase-immunoreactive cells by threefold. Together, we demonstrate that induced overexpression of transcription factor genes has profound and specific effects on the differentiation of rat and human midbrain progenitors, although few dopamine neurons are generated.



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Biological Process

  

Objects Annotated

Genes (Rattus norvegicus)
Pitx3  (paired-like homeodomain 3)


Additional Information