The CRHR1/CREB/REST signaling cascade regulates mammalian embryonic neural stem cell properties.
Mookwang KwonJu Hyun LeeYoungik YoonSamuel J PleasureKeejung YoonPublished in: EMBO reports (2022)
Growing evidence suggests that the corticotropin-releasing hormone (CRH) signaling pathway, mainly known as a critical initiator of humoral stress responses, has a role in normal neuronal physiology. However, despite the evidence of CRH receptor (CRHR) expression in the embryonic ventricular zone, the exact functions of CRH signaling in embryonic brain development have not yet been fully determined. In this study, we show that CRHR1 is required for the maintenance of neural stem cell properties, as assessed by in vitro neurosphere assays and cell distribution in the embryonic cortical layers following in utero electroporation. Identifying the underlying molecular mechanisms of CRHR1 action, we find that CRHR1 functions are accomplished through the increasing expression of the master transcription factor REST. Furthermore, luciferase reporter and chromatin immunoprecipitation assays reveal that CRHR1-induced CREB activity is responsible for increased REST expression at the transcriptional level. Taken together, these findings indicate that the CRHR1/CREB/REST signaling cascade plays an important role downstream of CRH in the regulation of neural stem cells during embryonic brain development.
Keyphrases
- stem cells
- transcription factor
- poor prognosis
- signaling pathway
- neural stem cells
- gene expression
- single cell
- binding protein
- high throughput
- immune response
- heart failure
- genome wide
- resting state
- cerebral ischemia
- cell therapy
- white matter
- crispr cas
- long non coding rna
- left ventricular
- high glucose
- dna damage
- functional connectivity
- oxidative stress
- blood brain barrier
- bone marrow
- density functional theory
- brain injury