c- and N-myc regulate neural precursor cell fate, cell cycle, and metabolism to direct cerebellar development.

The Cerebellum
Alice WeyPaul S Knoepfler

Abstract

Separate murine knockout (KO) of either c- or N-myc genes in neural stem and precursor cells (NSC) driven by nestin-cre causes microcephaly. The cerebellum is particularly affected in the N-myc KO, leading to a strong reduction in cerebellar granule neural progenitors (CGNP) and mature granule neurons. In humans, mutation of N-myc also causes microcephaly in Feingold Syndrome. We created a double KO (DKO) of c- and N-myc using nestin-cre, which strongly impairs brain growth, particularly that of the cerebellum. Granule neurons were almost absent from the Myc DKO cerebellum, and other cell types were relatively overrepresented, including astroglia, oligodendrocytes, and Purkinje neurons. These findings are indicative of a profound disruption of cell fate of cerebellar stem and precursors. DKO Purkinje neurons were strikingly lacking in normal arborization. Inhibitory neurons were ectopic and exhibited very abnormal GAD67 staining patterns. Also consistent with altered cell fate, the adult DKO cerebellum still retained a residual external germinal layer (EGL). CGNP in the DKO EGL were almost uniformly NeuN and p27KIP1 positive as well as negative for Math1 and BrdU at the peak of normal cerebellar proliferation at P6. The presenc...Continue Reading

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Citations

Nov 18, 2011·The Cerebellum·Ketty Leto, Ferdinando Rossi
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Tiemo J KlischHuda Y Zoghbi
Jul 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Alessandra GiorgettiJuan Carlos Izpisua Belmonte
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Methods Mentioned

BETA
acetylation
PCR

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