Comparison of mouse and human developing striatal gene expression

• Published in: Neuroreport Vol. 25; no. 3; pp. 162 - 163
• Main Authors: Vinh, N N, Kelly, C M, Heuer, A, Precious, S V, Allen, N D, Kemp, P J, Rosser, A E
• Format: Journal Article
• Language: English
• Published: 12-02-2014
• ISSN: 0959-4965; 1473-558X

Transplantation of neural cells derived from pluripotent stem cell sources in Huntington's disease requires that they be directed towards a medium spiny striatal DAPRPP-32 positive neuronal phenotype. There are published reports of protocols to direct the differentiation of cells to an MSN phenotype that have shown success in terms of DARPP-32 readout, but limited functional effect of these cells is available to date. This would suggest that DAPRPP-32 alone is not sufficient to confirm a mature functional MSN neuron. Thus, there is a need to both understand more about the signals required for MSN development and to identify a profile of markers that are indicative of normal MSN differentiation. To this end, we have carried out a molecular and histological comparison of human and mouse whole ganglionic eminence (WGE) development across the period during which MSNs are generated. We performed QPCR of a range of known and potential striatal differentiation markers of WGE cells between E12 and E16 in the mouse and 6-12 weeks post conception in the human, and have attempted to correlate the striatal development between the two species. We also performed in situ hybridization and immunohistochemical analysis of sections over a similar developmental range for both species. We carried out electrophysiological analysis of human WGE cells over the same developmental period. For the first time, this provides key information on the genetic stages of human MSN development, and highlights some key species differences.