Spatial And Temporal Distribution Of ADAM10 In Late Stage Of Embryonic Development In Mouse Cerebral Cortex

Mammals have the highly developed cerebral cortex, which plays a major role in regulating animal function. The cerebral cortex is developed from neural stem cells (NSCs) located at neuroectoderm. The NSCs differentiate into either neurons or glia cells, such processes are regulated by a large number of signaling molecules. Notch signaling has been considered as the critical molecular switch for neural stem cell fate. ADAM10(A disintegrin and metalloprotease10) is the critical rate-limiting S2enzyme for Notch receptor before it can be processed by gamma-secretase to generate the intracellular Notch domain (NICD), which functions as a transcription factor to promote downstream effects. Conditional ADAM10knockout in cortex under Nestin promoter can destroy the cortex layout as a consequence of lacking Notch signaling to maintain the undifferentiated NSCs pool from early cortex developmental stage. However, the function of AD AM10during late embryonic development is still not clear.We applied western blot, immunofluorescent staining, and in situ hybridization experiments on E14.5to P1mice cortex. Our results demonstrated that ADAM10expression is located at ventricular zone (VZ) and cortical plate (CP) during this period. Such expression pattern is correlates with NICD at mouse later embryonic cortex developmental stages. After knocking down the expression of ADAM10during E14to E18in mice at VZ, the neocortex become thinner and the VZ layer is severly deformed. This result correlates with ADAM10-Notch function in maintaining NSCs pool at VZ layer. We also examined the expression of Nestin for NSCs, Tuj1for differentiated neurons, and S100β for glia cells. The expression region of ADAM10is partially colocalized with Tuj1 and S100β at CP layer during E16.5to P1. Such expression pattern correlates with the neuron maturation and gliogenesis process in late embryonic to postnatal neocortex. Therefore, ADAM10-Notch signaling probably has functions during neuron maturation and gliogenesis during late embryonic cortex development stages.