Opera Medica et Physiologica

Samuel J. Pleasure

Interaction of Emx2 and Shh to Modulate the Embryonic Neural Stem Cells of the Ventral Hippocampus

Neurogenesis is one of the most striking phenomena in the adult rodent brain, however, it is limited to only particular brain regions including the olfactory bulb and the dentate gyrus (Altman, 1962; Altman, 1963). In the subventricular zone (SVZ) newborn neurons are produced and travel a long distance through the rostral migratory stream to reach the OB where they become diverse types of interneurons (Doetsch and Alvarez-Buylla, 1996; Doetsch et al., 1999; Lim and Alvarez-Buylla, 2016).

Abstract

In this study we examined the intersection of two molecular pathways both known to regulate dentate development – the Emx2 transcription factor and the Sonic Hedgehog (Shh) morphogenic scignaling pathway. We confirmed that Emx2 mutant mice have a markedly reduced dentate gyrus and studied evidence of changes in Shh signaling and Shh expression in these mutants. Our results indicate that loss of Emx2 affects the numbers and distribution of Gli+ ventrally derived dentate neural stem cells that are responsible for populating the perinatal dentate gyrus. Accompanying this, we find that Emx2 mutants have reduced expression of Shh in the amygdalo-hippocampal region. In addition, there are ectopic Shh responsive progenitors that fail to properly populate the dentate. Taken together our results indicate that Emx2 regulates dentate development in part by altering availability and signaling of Shh.

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PDF icon omp2018.003.0060.pdf2.86 MB

The Crossroads of Neural Stem Cell Development and Tumorigenesis

Overview of the Neurogenic and Tumorigenic Niche

Abstract

Isolated brain tumors contain cells that exhibit stem cell features and a tissue microenvironment bearing remarkable similarities to the normal neurogenic niche. This supports the idea that neural stem (NSCs) or progenitor cells, and their progeny are the likely tumor cell(s) of origin. This prompted the investigation of the relationship between NSCs/progenitors and the initiation of tumorigenesis. These studies led to the identification of common signaling machineries underlying NSC development and tumor formation, particularly those with known roles in proliferation and cell fate determination. This review will explore the molecular mechanisms that regulate NSC behavior in the neurogenic niche of the forebrain, and how deregulation of the developmental potential of NSCs might contribute to tumorigenesis. 

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PDF icon OMP_2016_03_0040.pdf1.56 MB
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