Periodic Reporting for period 1 - mAMBo (The role of ASCL1 and MYCN in human brain development)
Reporting period: 2019-05-01 to 2021-04-30
1) Firstly, identification of neural cell types expressing MYCN in both human foetal brains and cortical brain organoids to establish the expression pattern of MYCN during brain development in humans.
2) Secondly, human embryonic stem cells were grown in culture after removal of the MYCN gene, and consequently differentiated into neural progenitors and neurons, to see the effects of MYCN in neurogenesis, the process by which neurons are formed.
Work from part 1 produced a detailed analysis of MYCN expression during human neurogenesis at different developmental times. Results from part 2 demonstrated that MYCN contributes to neurogenesis by promoting the differentiation of neural progenitors into neurons. However, the absence of MYCN in human embryonic stem cells was associated with an increase of C-MYC expression, suggesting that another MYC gene could be taking over MYCN’s role in earlier stages of neurogenesis. Together, the project results have been explored in further research to determine how mutations in MYCN gene cause brain disorders and whether other MYC genes could be able to compensate for the loss of MYCN during neurogenesis. These findings have been reported to the research community informally prior to be being submitted for publication in a peer-reviewed scientific journal with open access, upon completion of the research project.