New insights in the regulation of the devloping forebrain
June 2017: Prof David Price and his team shed further lights into the molecular network during brain development.
Our brain is responsible for many functions such as sensory and motion control, consciousness and cognition. Building a functional brain needs co-ordination of a set of protein called transcription factors. Transcription factors regulate their target genes tightly both in time and regions.
Pax6 is one of these transcription factors, its functions have been found important in the development of forebrain, which consists of neocortex, hypothalamus, hippocampus and thalamus. Insufficient PAX6 protein in human causes aniridia, or absence of iris.
Scientists adopt mice carrying the same mutation in human PAX6-insufficient patients as an experimental model. In mouse cortex, previous study has showed that the expression pattern of Pax6 protein is high rostro-laterally and low caudo-medially and this gradient is important for cortical development.
Also in the cortex, a gene called Cell division cycle associated 7 (Cdca7) was identified as a potential downstream target of Pax6 regulation.
In this study, the expression of Cdca7 showed a counter-gradient against that of Pax6 at mouse embryonic stage E12.5 to E15.5. Furthermore the expression of Cdca7 was increased in mice lacking functional Pax6 protein, indicating that Pax6 may negatively control the expression of Cdca7.
The function of Cdca7 in cortical development has not been previously investigated. Using a technique called in utero electroporation, the Cdca7 protein can be overexpressed to allow the team around David Price to investigate its function. In E12.5 mice embryos, overexpression of Cdca7 protein caused decreased production of intermediate progenitor cells, one of the two main progenitors in the cortex. In addition, production of neurons was also reduced by the overexpression of Cdca7 at E12.5.
Taken together, Cdca7 may affect differentiation of radial glia cells into neurons during cortical development.