Transcriptional Regulation of Notch1 Expression by Nkx6.1 in Neural Stem/Progenitor Cells during Ventral Spinal Cord Development

被引：16

作者：

Li, Ying ^{[1
]}

Tzatzalos, Evangeline ^{[1
,3
]}

Kwan, Kelvin Y. ^{[2
]}

Grumet, Martin ^{[2
]}

Cai, Li ^{[1
]}

机构：

[1] Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA

[2] Rutgers State Univ, Dept Cell Biol & Neurosci, WM Keck Ctr Collaborat Neurosci, 604 Allison Rd, Piscataway, NJ 08854 USA

[3] Wilson Sonsini Goodrich & Rosati, Seattle, WA 98104 USA

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

关键词：

MOTOR-NEURON; GENE-EXPRESSION; NERVOUS-SYSTEM; SONIC HEDGEHOG; STEM-CELL; INTERNEURON; FATE; ORIGIN; DIVERSITY; PATTERN;

D O I：

10.1038/srep38665

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Notch1 signaling plays a critical role in maintaining and determining neural stem/progenitor cell (NSPC) fate, yet the transcriptional mechanism controlling Notch1 specific expression in NSPCs remains incomplete. Here, we show transcription factor Nkx6.1 interacts with a cis-element (CR2, an evolutionarily conserved non-coding fragment in the second intron of Notch1 locus) and regulates the expression of Notch1 in ventral NSPCs of the developing spinal cord. We show that the Notch1 expression is modulated by the interaction of Nkx6.1 with a 139 bp enhancer sequence within CR2. Knockdown or overexpression of Nkx6.1 leads to down-or up-regulated Notch1 expression, respectively. In CR2-GFP transgenic mouse, GFP expression was found prominent in the ventricular zone and neural progenitor cells from embryonic day 9.5 to postnatal day 7. GFP+ cells were mainly neural progenitors for interneurons and not for motoneurons or glial cells. Moreover, GFP expression persisted in a subset of ependymal cells in the adult spinal cord, suggesting that CR2 is active in both embryonic and adult NSPCs. Together our data reveal a novel mechanism of Notch1 transcriptional regulation in the ventral spinal cord by Nkx6.1 via its binding with Notch1 enhancer CR2 during embryonic development.

引用

页数：13

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