A model of neocortical area patterning in the lissencephalic mouse may hold for larger gyrencephalic brains

Abstract

In the mouse, two telencephalic signaling centers orchestrate embryonic patterning of the cerebral cortex. From the rostral patterning center in the telencephalon, the Fibroblast Growth Factor, FGF8, disperses as a morphogen to establish the rostral to caudal axis of the neocortical area map.FGF8 coordinates with Wnt3a from the cortical hem to regulate graded expression of transcription factors that position neocortical areas, and control hippocampal development. Whether similar signaling centers pattern the much larger cortices of carnivore and primate species, however, is unclear. The limited dispersion range of FGF8 and Wnt3a is inconsistent with patterning larger cortical primordia. Yet the implication that different mechanisms organize cortex in different mammals flies in the face of the tenet that developmental patterning mechanisms are conserved across vertebrate species. In the present study, both signaling centers were identified in the ferret telencephalon, as were expression gradients of the patterning transcription factor genes regulated by FGF8 and Wnt3a. Notably, at the stage corresponding to the peak period of FGF8 signaling in the mouse neocortical primordium (NP), the NP was the same size in ferret and mouse, which would allow morphogen patterning of the ferret NP. Subsequently, the size of ferret neocortex shot past that of the mouse. Images from online databases further suggest that NP growth in humans, too, is slowed in early cortical development. We propose that if early growth in larger brains is held back, mechanisms that pattern the neocortical area map in the mouse could be conserved across mammalian species. K E Y W O R D Scerebral cortex, embryonic patterning, Ferret, FGF8, morphogen, mouse, neocortical area map, RRID:AB_514497, RRID:SCR 003070, Wnt3a

Early dorsomedial tissue interactions regulate gyrification of distal neocortex

“…In mice, this pathway operates to prevent differential expansion of cortical progenitors and suppress gyrification of the distant neocortex. It has been recently demonstrated that similar to the mouse, a Wnt3a-expressing signaling center is also present in the DMe of the naturally gyrencephalic ferret 56 . Although the mechanisms that regulate DMe development and signaling in gyrencephalic mammals remain unknown, in the developing human neocortex, expression of Wnt receptor FZD8 is higher than in the mouse and even the chimpanzee, potentially making the developing human neocortex particularly sensitive to dynamics of Wnt signaling 57 .…”

Evaluation of advances in cortical development using model systems

“…However, these molecules have dispersion ranges maxing at a few hundred microns (Parchure et al., 2018). A recent study of these patterning mechanisms in the developing ferret cortex found that FGF and Wnt gradients and patterning centers were recapitulated (Jones et al., 2019). Importantly, the length of the developing neocortex along the anterior–posterior axis at the time of FGF‐induced patterning was comparable between ferrets and mice of equivalent developmental stages (Jones et al., 2019).…”

“…A recent study of these patterning mechanisms in the developing ferret cortex found that FGF and Wnt gradients and patterning centers were recapitulated (Jones et al., 2019). Importantly, the length of the developing neocortex along the anterior–posterior axis at the time of FGF‐induced patterning was comparable between ferrets and mice of equivalent developmental stages (Jones et al., 2019). However, ferret cortical expansion accelerated after these initial patterning stages (Jones et al., 2019).…”

“…Importantly, the length of the developing neocortex along the anterior–posterior axis at the time of FGF‐induced patterning was comparable between ferrets and mice of equivalent developmental stages (Jones et al., 2019). However, ferret cortical expansion accelerated after these initial patterning stages (Jones et al., 2019). This hypothesis suggests that the patterning mechanisms in the mice may be recapitulated in larger mammals such as humans, if there is a similar delay in cortical expansion in human development (Jones et al., 2019).…”

“…However, ferret cortical expansion accelerated after these initial patterning stages (Jones et al., 2019). This hypothesis suggests that the patterning mechanisms in the mice may be recapitulated in larger mammals such as humans, if there is a similar delay in cortical expansion in human development (Jones et al., 2019).…”