Fine-tuning of cortical progenitor proliferation by thalamic afferents.

Abstract

During cerebral cortical cortex neurogenesis two major types of progenitors generate a variety of morphologically and functionally diverse projection neurons destined for the different cortical layers in non-gyrified mice. Radial glia cells (RGCs) undergo mitosis in the cortical ventricular zone and exhibit an apical-basal cell polarity, whereas non-polar intermediate progenitor cells (IPCs) divide basally in the subventricular zone (Franco and Muller, 2013; Taverna et al., 2014). The contribution of these cortical progenitor subtypes to particular cortical layers remains debated. Several lines of evidence suggest that IPCs give rise to the majority of cortical neurons, while only 10–20 % are directly generated by apical progenitors (Franco and Muller, 2013). The generation of excitatory cortical neurons follows a temporal order with deep layer neurons born first and upper layers are generated successively during later stages of neurogenesis. Furthermore, the symmetry of mitotic division is instructive for the prospective fate of daughter cells and thus for their laminar destination (Taverna et al., 2014). Various intrinsic and extrinsic cues have been identified that regulate the division mode and cell fate of cortical precursors. In addition to intra-cortical control of cortical neurogenesis such as paracrine interactions between progenitor cells (North et al., 2009) and feedback signaling from post-mitotic neurons of the cortical plate (Seuntjens et al., 2009), extra-cortical signals exerting control over cortical proliferation are increasingly attracting attention. These include factors from the cortico-spinal fluid (Lehtinen and Walsh, 2011) or invading glutamatergic neurons (Teissier et al., 2012). However, the impact of invading thalamo-cortical axons on cortical neurogenesis and layer formation remains largely unknown. Previous in vitro studies suggested that thalamic fibres regulate cell cycle properties and division mode by releasing soluble factors (Dehay et al., 2001). In turn, our data show a contact-mediated extra-cortical regulation of cortical neurogenesis by invading thalamic afferents (Figure 1) (Gerstmann et al., 2015).