scholarly journals Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons

2019 ◽  
Vol 29 (11) ◽  
pp. 4831-4849 ◽  
Author(s):  
Teng Guo ◽  
Guoping Liu ◽  
Heng Du ◽  
Yan Wen ◽  
Song Wei ◽  
...  

Abstract Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2F/− mice), GSX2+ and ASCL1+ neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1, and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development.

Stem Cells ◽  
2021 ◽  
Vol 39 (7) ◽  
pp. 929-944
Author(s):  
Naoya Yuizumi ◽  
Yujin Harada ◽  
Takaaki Kuniya ◽  
Takehiko Sunabori ◽  
Masato Koike ◽  
...  

2012 ◽  
Vol 29 (5) ◽  
pp. 828-842 ◽  
Author(s):  
Aminul I. Ahmed ◽  
Anan B. Shtaya ◽  
Malik J. Zaben ◽  
Emma V. Owens ◽  
Clemens Kiecker ◽  
...  

2011 ◽  
Vol 286 (18) ◽  
pp. 16321-16331 ◽  
Author(s):  
Eva Hennen ◽  
Tim Czopka ◽  
Andreas Faissner

There is increasing evidence that the stem and progenitor cell population that builds the central nervous system is very heterogeneous. Stem cell markers with the potential to divide this cell pool into subpopulations with distinct characteristics are sparse. We were looking for new cell type-specific antigens to further subdivide the progenitor pool. Here, we introduce the novel monoclonal antibody clone 5750. We show that it specifically labels cell surfaces of neural stem and progenitor cells. When 5750-expressing cells were isolated by fluorescence-activated cell sorting from embryonic mouse brains, the sorted population showed increased neurosphere forming capacity and multipotency. Neurospheres generated from 5750-positive cells could self-renew and remained multipotent even after prolonged passaging. Carbohydrate binding assays revealed that the 5750 antibody specifically binds to LewisX-related carbohydrates. Interestingly, we found that the LewisX epitope recognized by clone 5750 differs from those detected by other anti-LewisX antibody clones like 487LeX, SSEA-1LeX, and MMALeX. Our data further reveal that individual anti-LewisX clones can be successfully used to label and deplete different subpopulations of neural cells in vivo and in vitro. In conclusion, we present a new tool for the isolation and characterization of neural subpopulations and provide insights into the complexity of cell surface glycosylation.


2008 ◽  
Vol 28 (9) ◽  
pp. 1530-1542 ◽  
Author(s):  
Tamara Roitbak ◽  
Lu Li ◽  
Lee Anna Cunningham

Vascular cells provide a neural stem/progenitor cell (NSPC) niche that regulates expansion and differentiation of NSPCs within the germinal zones of the embryonic and adult brain under both physiologic and pathologic conditions. Here, we examined the NSPC—endothelial cell (NSPC/EC) interaction under conditions of ischemia, both in vitro and after intracerebral transplantation. In culture, embryonic mouse NSPCs supported capillary morphogenesis and protected ECs from cell death induced by serum starvation or by transient oxygen and glucose deprivation (OGD). Neural stem/progenitor cells constitutively expressed hypoxia-inducible factor 1α (HIF-1α) transcription factor and vascular endothelial growth factor (VEGF), both of which were increased approximately twofold after the exposure of NSPCs to OGD. The protective effects of NSPCs on ECs under conditions of serum starvation and hypoxia were blocked by pharmacological inhibitors of VEGF signaling, SU1498 and Flt-1-Fc. After intracerebral transplantation, NSPCs continued to express HIF-1α and VEGF, and promoted microvascular density after focal ischemia. These studies support a role for NSPCs in stabilization of vasculature during ischemia, mediated via HIF-1α-VEGF signaling pathways, and suggest therapeutic application of NSPCs to promote revascularization and repair after brain injury.


Author(s):  
Linda C. Hassinger ◽  
James E. Crandall

We have begun to look directly at small numbers of afferent axons to early generated neurons that form the preplate in the developing mouse cortex. The carbocyanine dye Dil (1’1, dioctadecyl-3,3,3’3’-tetramethyl-indocarbocyanine) has proved especially useful for this goal. DiI labels axons and their terminals with greater sensitivity and without some of the disadvantages of axon filling with HRP. The increased sensitivity provided by labeling embryonic axons with DiI has given us new insights into the development of cortical afferents. For instance, we reported originally that afferents from the thalamus were present below the cortex as early as embryonic day 15 (E15) based on HRP injections into mouse embryos. By using DiI placements into the thalamus in aldehyde-fixed brains, we now know that thalamic fibers reach the cortex 24 hrs earlier.


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