Master of Science (MS)
Corticogenesis, Cux2, Fezf2, Neurodevelopment, Radial Glial Cells, Stem Cells
Biology; Neurosciences; Developmental biology
The mammalian neocortex is 6-layered structure that develops in an “inside-out” manner, with cells of the deep layers (Layers 5-6) born first. Cells of the superficial outer layers (Layers 2-4) are generated subsequently and must migrate past older born cells to their final laminar position. Pioneering transplant studies suggested a progressive lineage restriction model, which posits that early neural stem cells (or radial glial cells, RGCs) are multipotent and sequentially generate different types of cortical neurons based on birthdate. Recently published work from Franco et al. (2012) argues against this paradigm, and proposes the existence of a subclass of neural stem cells, fated from an early embryonic age to produce exclusively upper-layer neurons. They contend that at mouse embryonic day 10.5 (E10.5), when neocortical genesis is just beginning, an RGC subpopulation marked by expression of genetic transcription factor cut-like homeobox 2 (Cux2) is fated to produce exclusively upper layer (L2-4) cells. Cells not expressing Cux2 are fated to become deep layer (L5-6). We recently published work testing this model using Cre-mediated recombination. Our experiments demonstrated that both clonal and population levels of Cux2+ and Fezf2+ RGCs produce progeny that are multipotent and able to generate neurons, astrocytes, and oligodendrocytes. Here, we extend our lab’s previous work of the Cux2-positive and Fezf2-positive RGC lineages and find that E10.5 neocortical progenitors are able to generate diverse neuronal subtypes located throughout layers 2-6 as well as macroglia. Collectively, we find that Cux2-positive RGCs development does not differ from the progressive lineage restriction theory, and does not support the cell-intrinsic theory postulated by Franco et al. (2012).
Nguyen, Ton Dan, "Cux2-Positive Radial Glial Cells Generate Diverse Subtypes of Neocortical Projection Neurons and Macroglia" (2016). Master's Theses. 4732.