Neocortex Patterning by the Secreted Signaling Molecule FGF8

Abstract

A classic model proposes that the mammalian neocortex is divided into areas early in neurogenesis, but the molecular mechanisms that generate the area map have been elusive. Here we provide evidence that FGF8 regulates development of the map from a source in the anterior telencephalon. Using electroporation-mediated gene transfer in mouse embryos, we show that augmenting the endogenous anterior FGF8 signal shifts area boundaries posteriorly, reducing the signal shifts them anteriorly, and introducing a posterior source of FGF8 elicits partial area duplications, revealed by ectopic somatosensory barrel fields. These findings support a role for FGF signaling in specifying positional identity in the neocortex.

The olfactory bulb as an independent developmental domain

“…88,89 Furthermore, if the strong morphogenetic agent FGF8 is ectopically expressed in the posterior telencephalon before the arrival of thalamic axons, the somatosensory cortex is partially duplicated, and an additional population of thalamic axons develops to innervate these extra barrels. 2 Factors extrinsic to the developing cortex (the arrival of thalamo-cortical fibers) have also been shown to control the specification of the different cortical areas. 90 An extension to the protomap hypothesis leads us to consider the regional expression in other telencephalic structures in the absence of a patterned afferent input.…”

“…In the`protomap' model, cortical regions are patterned prior to the migration of the newborn neurons (intrinsic control), 1 an event presumably specified by important molecular determinants. 2 In this model, the arrival of innervating axons would merely serve to modify and refine the protomap (an important facet of maintenance). In the second model, the`protocortex' theory, the newborn cortical neurons are a homogeneous cell population, that later on in corticogenesis are patterned into the distinct areas by the specific cues supplied by axons growing in from the thalamus (extrinsic control).…”

Somatosensory cortical plasticity: recruiting silenced barrels by active whiskers

“…Several lines of evidence indicate that somatosensory periphery-related neural maps and patterns are conveyed to target cells by the afferents at each synaptic relay station Jhaveri, 1990, 1992a,b;Erzurumlu and Killackey, 1983;Senft and Woolsey, 1991). Current understanding is that topographically organized projections (somatotopic maps) along the somatosensory system are established via several axon guidance cues independent of neural activity Fukuchi-Shimogori and Grove, 2001;Maier et al, 1999;Vanderhaeghen et al, 2000). On the other hand, patterning of neural connections within "somatotopic" maps is controlled by neural activity-mediated mechanisms (Erzurumlu and Kind, 2001).…”

Gene Therapy Progress and Prospects: Electroporation and other physical methods

“…[29][30][31] Using very fine electrodes, it is possible to deliver plasmids to defined regions of the developing brain to track cell migration and to modify patterns of development. Recently, Wei et al 32 have extended this technology to adult rodents, showing that it is possible to express selectively plasmid-based constructs in specific regions of the adult CNS.…”