Figure 4.

Diagram of the TC pathway and barrel formation in mice. Waves of calcium signals in the embryonic thalamus, schematically illustrated by graded colors, are suggested to correspond to a somatotopic connectivity between the thalamus and barrel cortex, before sensory input is present. Without these waves, barrel cortex becomes hyperexcitable and does not develop columnar and barrel organization (Antón-Bolaños et al., 2019). Developing TC axons are guided to cortex through multiple molecular guidance cues, some attractive and some repulsive (Antón-Bolaños et al., 2018). Morphogens and signaling molecules set up areal specification of the neocortex into primary sensory, motor, and association cortex areas (Fukuchi-Shimogori and Grove, 2001; Assimacopoulos et al., 2012; Zembrzycki et al., 2013, 2015; Stocker and O'Leary, 2016). In the developing barrel cortex, a patchwork of spontaneous activity corresponds to barrels at the time of their formation (Mizuno et al., 2018). Layer- and projection-type-specific identity of neocortical neurons is determined by their time of differentiation and specific transcription factors (Greig et al., 2013; Govidan and Jabaudon, 2017). Transcription factor RORα is cell-autonomously required in the thalamus for clustering of TC axons and dendritic maturation of layer 4 neurons in the barrel cortex (Vitalis et al., 2018). Dendritic orientation of barrel cells is controlled by the BTBD3 transcription factor (Matsui et al., 2013), and BTBD3 appears to be controlled by the transcription factor Lhx2 (Wang et al., 2017). So, transcription factors play multiple roles from cell specification to dendritic orientation in the barrel cortex.