Area Patterning of the Mammalian Cortex

Abstract

Here we describe mechanisms regulating area patterning of developing mammalian neocortex, referred to as arealization. Current findings indicate an interplay between intrinsic genetic mechanisms and extrinsic information relayed to cortex by thalamocortical input. Intrinsic mechanisms are based on morphogens and signaling molecules secreted by patterning centers, positioned at the perimeter of dorsal telencephalon, that generate across nascent cortex the graded expression of transcription factors in cortical progenitors. Two major patterning centers are the commissural plate, which expresses Fgf8 and Fgf17, and the cortical hem, which expresses Bmps and Wnts. Four transcription factors, COUP-TFI, Emx2, Pax6, and Sp8, with graded expression across the embryonic cortical axes, are shown to determine sizes and positions of cortical areas by specifying or repressing area identities within cortical progenitors. They also interact to modify their expression, as well as expression of Fgf8. We review these mechanisms of arealization and discuss models and concepts of cortical area patterning.

Thalamic WNT3 Secretion Spatiotemporally Regulates the Neocortical Ribosome Signature and mRNA Translation to Specify Neocortical Cell Subtypes

“…Neocortical development is defined by precise spatiotemporal control of protein expression and activity that drives the formation of complex cellular networks (Molyneaux et al, 2007;Leone et al, 2008;Kriegstein and Alvarez-Buylla, 2009;Rakic, 2009;Breunig et al, 2011;Kwan et al, 2012b;DeBoer et al, 2013). Mouse neocortical neurogenesis from radial glial stem cells occurs between embryonic day (E) 11 and E18, followed by gliogen-esis.…”

“…We further present an analysis of functionally related mRNA subsets that differentially associate with polysomes during neocortical development, including mRNAs encoding proteins involved in translation and transcription. One such neuronal transcription factor, Forkhead box protein P2 (Foxp2;Ferland et al, 2003;Groszer et al, 2008), and a regulator of oligodendrocyte development, Adenomatous polyposis coli (Apc, also known as CC-1; Jablonska et al, 2012;Lang et al, 2013), are likewise under translational control by thalamic WNT3. The ability of timed signals from in-growing axons to define the combinatorial composition of the ribosome and translation of specific mRNAs is a mechanism that may contribute to the spatial and temporal patterning of the CNS.…”

Endocannabinoids via CB1receptors act as neurogenic niche cues during cortical development

“…The developing nervous system is characterized by highly active and dynamically regulated cellular processes involving cell generation and differentiation, migration to their final destination, neuronal maturation and establishment of appropriate neuronal connectivity [1,2]. The precise regulation of these processes is achieved by a complex network of intrinsic molecular determinants and intracellular signalling pathways that are in turn modulated by surrounding information from the neurogenic niche [3].…”

FIIND: Ferret Interactive Integrated Neurodevelopment Atlas

“…The development of a human brain is the proliferation and migration of billions of cells (Bystron et al 2008) followed by the formation of interconnections (Innocenti and Price 2005) between brain regions by way of molecular guidance and activity dependent processes (O'Leary et al 2007). The high degree of conservation of developmental mechanisms makes it possible to use animal models to study the molecular aspects of human diseases.…”