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Journal Article

Scratch2 modulates neurogenesis and cell migration through antagonism of bHLH proteins in the developing neocortex.

MPS-Authors
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Paul,  V.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Tonchev,  A. B.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Pavlakis,  E.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Stoykova,  A.
Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

1569533.pdf
(Publisher version), 4MB

Supplementary Material (public)

1569533-Suppl-1.doc
(Supplementary material), 95KB

1569533-Suppl-2.tif
(Supplementary material), 402KB

1569533-Suppl-3.tif
(Supplementary material), 10MB

1569533-Suppl-4.tif
(Supplementary material), 14MB

1569533-Suppl-5.tif
(Supplementary material), 8MB

1569533-Suppl-6.tif
(Supplementary material), 14MB

1569533-Suppl-7.tif
(Supplementary material), 9MB

1569533-Suppl-8.tif
(Supplementary material), 28MB

1569533-Suppl-9.tif
(Supplementary material), 4MB

Citation

Paul, V., Tonchev, A. B., Henningfeld, K. A., Pavlakis, E., Rust, B., Pieler, T., et al. (2014). Scratch2 modulates neurogenesis and cell migration through antagonism of bHLH proteins in the developing neocortex. Cerebral Cortex, 24(3), 754-772. doi:10.1093/cercor/bhs356.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0010-226A-B
Abstract
Scratch genes (Scrt) are neural-specific zinc-finger transcription factors (TFs) with an unknown function in the developing brain. Here, we show that, in addition to the reported expression of mammalian Scrt2 in postmitotic differentiating and mature neurons in the developing and early postnatal brain, Scrt2 is also localized in subsets of mitotic and neurogenic radial glial (RGP) and intermediate (IP) progenitors, as well as in their descendants—postmitotic IPs and differentiating neurons at the border subventricular/intermediate zone. Conditional activation of transgenic Scrt2 in cortical progenitors in mice promotes neuronal differentiation by favoring the direct mode of neurogenesis of RGPs at the onset of neurogenesis, at the expense of IP generation. Neuronal amplification via indirect IP neurogenesis is thereby extenuated, leading to a mild postnatal reduction of cortical thickness. Forced in vivo overexpression of Scrt2 suppressed the generation of IPs from RGPs and caused a delay in the radial migration of upper layer neurons toward the cortical plate. Mechanistically, our results indicate that Scrt2 negatively regulates the transcriptional activation of the basic helix loop helix TFs Ngn2/NeuroD1 on E-box containing common target genes, including Rnd2, a well-known major effector for migrational defects in developing cortex. Altogether, these findings reveal a modulatory role of Scrt2 protein in cortical neurogenesis and neuronal migration.