Chapter 23 Transplantation of brain tissue from murine trisomy 16 into euploid hosts: Effects of gene imbalance on brain development

This chapter describes preliminary results from studies involving the transplantation of cortex from trisomy 16 (Ts16) and euploid littermates at days 15/16 of gestation (E15/16) into neonatal euploid hosts. Aside from the histological analysis of Nissl stained sections, acetylcholinesterase (AChE) expressing fibers is visualized as a presynaptic marker for developing cholinergic innervations from the basal forebrain. In addition, immunocytochemical and/ or in situ hybridization methods have been used to visualize the expression and gene product of growth associated protein 43 (GAP43) and preprosomatostatin (ppSmst). GAP43, also known as F1, PP46, and B50, is expressed in association with axon growth during development, regeneration, and plasticity; and therefore, it may play an important role in postmitotic neuronal differentiation. Somatostatin (Smst), on the other hand, shows a transient peak of expression during the second and third weeks after birth, the period of cortical cell differentiation and synapse formation. Furthermore, Smst expression appears to be regulated, in part, by cholinergic innervations. Many of the cells expressing Smst during cortical development are probably members of a class of early subplate neurons of the Cajal–Retzius type. These neurons presumably play a transient role in cortical morphogenesis and appear to die as development proceeds. Quantifications of the mitochondrial RNA (mRNA) for both GAP43 and ppSmst indicate that they are over-expressed in Ts16 fetal brains, in levels consistent with a simple gene dosage effects. The chapter discusses the role of the host brain in correcting the overexpression of these 2 genes in the cortical grafts.