Concurrent Generation of Subplate and Cortical Plate Neurons in Developing Trisomy 16 Mouse Cortex

Abstract

During embryonic development of the mammalian cerebral cortex, the generation of the marginal zone (MZ) and subplate (SP) precedes that of the cortical plate (CP). MZ and SP neurons are believed to play a ‘pioneering’ role in directing the organization of the CP and the specificity of connections between the CP and other brain regions. Here we report that this sequential order of neurogenesis is disrupted in the trisomy 16 (Ts16) mouse, a potential animal model of Down syndrome. Bromodeoxyuridine labeling was used to establish the date of generation of postmitotic SP and CP neurons in the somatosensory cortex. As has been previously reported, most SP neurons in euploid (control) cortex were generated on embryonic day 12.5 (E12.5), and production of CP neurons began a day later. In contrast, in the Ts16 cortex, few SP neurons were born on E12.5 and most were generated on E13.5 and E14.5 when CP neurons were also being produced. Thus, in the Ts16 cortex, many CP neurons are born and arrive at their destinations before the normal complement of SP neurons is present. This disruption of the temporal sequence of SP and CP generation may, therefore, interfere with the pioneering functions of the SP during cortical neurogenesis and may alter the connectivity of the cortex. Indeed, using lipophilic membrane tracers to label axonal projections, we found very little thalamocortical innervation of the Ts16 SP at an age when there is extensive innervation of the euploid SP.