Laminar Patterning in the Developing Neocortex by Temporally Coordinated Fibroblast Growth Factor Signaling

Abstract

Laminar organization, a fundamental neural architecture in the CNS, is a prominent feature of the neocortex, where the cortical neurons in spatially distinct layers are generated from the common progenitors in a temporally distinct manner during development. Despite many advances in the characterization of the molecular mechanisms of the radial migration of cortical neurons, the way in which the early-late temporal sequence of cortical neuron generation is linked with the deep-superficial spatial sequence of cell body positioning remains obscure. Using in vivo electroporation-mediated gene transfer, we show here that the activities mediated by fibroblast growth factor receptors (FGFRs) in cortical progenitors are critical for conferring proper migratory properties on nascent neuronal progeny. Furthermore, we provide supportive evidence that Pea3 subfamily members of Ets (Pea3-Ets) transcription factors mediate the activities of FGFR at the mid to late phase of neocortical development. In addition, using FGF18 knock-out mice, we demonstrate that FGF18 expressed by early-generated cortical neurons in the cortical plate is critical for the expression of Pea3-Ets transcription factors and that FGF18 is sufficient to induce their expressions. Our results thus imply that a feedback mechanism mediated by FGF signaling is involved in setting up the proper laminar positioning of cortical neurons; FGF18 derived from early-generated cortical neurons acts on the cortical progenitors expressing FGFRs and induces the expression of Pea3-Ets transcription factors that, in turn, confer proper migratory behaviors on nascent cortical progeny during the mid to late stages of neocortical development.

Opposing Fgf and Bmp activities regulate the specification of olfactory sensory and respiratory epithelial cell fates

“…Stage 12, 17 and 21 chick embryos were electroporated in the olfactory placodal/epithelial region with pCaggs-GFP (0.75 mg/ml) (Andersson et al, 2006) alone, or together with pMiwIII-noggin (Timmer et al, 2002), pMiwIII-Alk6 (James and Schultheiss, 2005), pCaggs-Fgfr3c-⌬C (Hasegawa et al, 2004) or pCaggs-Fgf8b (Delfini et al, 2005), all at 1.0 mg/ml. DNA was transferred using an Electro Square Porator ECM 830 (BTX Inc.).…”

Directing traffic in neural cells: determinants of receptor tyrosine kinase localization and cellular responses

“…Survival and proliferation of cortical astrocytes (Sibilia et al 1998;Wagner et al 2006); Astrocyte development and neuronal survival (Kornblum et al 1998 Regulation of neural tube development (Deng et al 1997;Hasegawa et al 2004); OL differentiation (Zhou et al 2006) p75NTR Negative regulation of hippocampal pyramidal neuron dendritic morphology and neurite outgrowth (Zagrebelsky et al 2005); Schwann cell migration, remyelination (Bentley and Lee 2000;Song et al 2006;Tomita et al 2007) TrkA Development of sensory sympathetic and cholinergic neurons Fagan et al 1996) TrkB Development of motor and/or sensory neurons (Ernfors et al 1994;Klein 1994;Pinon et al 1996); Interneuron migration (Polleux et al 2002) TrkC Development of sensory neurons Liebl et al 1997) 1998; Hirota et al 2004), in which cytoplasmic domains of the receptor are no longer accessible to signaling proteins, rendering the receptor signaling incompetent. Moreover, the increasingly acidic lysosomal environment ( pH 4.0) promotes protein degradation.…”

Validating in utero electroporation for the rapid analysis of gene regulatory elements in the murine telencephalon

“…Future studies can thus be performed to assess the importance of this Pax6 site for the pallial activity of the zER812-and 1.5-kb fragments. In addition, the expression of mouse (Hasegawa et al, 2004) and Xenopus (Chen et al, 1999;Munchberg and Steinbeisser, 1999) ER81 orthologues are regulated by fibroblast growth factor (FGF) signaling, whereas zebrafish ER81 expression appears to be FGFindependent (Roussigne and Blader, 2006). This suggests that the regulatory interactions governing ER81 expression were altered after terrestrial vertebrates branched off from fish 365 million years ago (Carroll, 1999).…”