FMRP regulates the transition from radial glial cells to intermediate progenitor cells during neocortical development.

“The RGC-to-IPC transition, a key step in neuronal production from RGCs, may underlie the evolutionary expansion of the cerebral cortex (Fish et al., 2008; Kriegstein and Alvarez-Buylla, 2009).”

“To overcome this problem, we used Lifeact-EGFP (Riedl et al., 2008, 2010), a fusion protein comprised of an F-actin binding domain and EGFP, to visualize the ring-like F-actin structure in transfected RGCs (Fig.”

“The I304N mutation impairs the association of FMRP with RNA (Bassell and Warren, 2008) and renders the protein a null mutant (Zang et al., 2009).”

“Moreover, potential function of FMRP in RGCs may be masked in Fmr1 knock-out embryos by compensation, which often occurs in constitutive knock-out mice (Deuel et al., 2006; Koizumi et al., 2006; Fasano et al., 2007; Satyanarayana and Kaldis, 2009).”

“Immediately following mCherry electroporation, EGFP should label cells with reduced levels of FMRP, because FMRP shRNA was coelectroporated with pCAX-EGFP 2 d before, and mCherry should label RGCs because in utero electroporation leads to specific transfection of RGCs (Gal et al., 2006).”

“These three proteins have similar domain structures and interact with each other (Zhang et al., 1995).”

“To overcome this problem, we used Lifeact-EGFP (Riedl et al., 2008, 2010), a fusion protein comprised of an F-actin binding domain and EGFP, to visualize the ring-like F-actin structure in transfected RGCs (Fig.”

“FMRP maintains the RGC pool by regulating the actin cytoskeleton Previous studies indicate that FMRP may regulate neuronal function by an actin-dependent mechanism (Schenck et al., 2003; Reeve et al., 2005).”

“Moreover, potential function of FMRP in RGCs may be masked in Fmr1 knock-out embryos by compensation, which often occurs in constitutive knock-out mice (Deuel et al., 2006; Koizumi et al., 2006; Fasano et al., 2007; Satyanarayana and Kaldis, 2009).”

“Thus, the transition from RGCs to IPCs plays a key role in determining the total number of neurons produced from RGCs and may underlie the evolutionary expansion of the cerebral cortex (Fish et al., 2008; Kriegstein and Alvarez-Buylla, 2009).”

“Several actin-dependent cellular mechanisms may control the cell fate decision of RGC divisions, including the regulation of apical polarity, interkinetic nuclear migration, and cleavage plane (Farkas and Huttner, 2008; Fish et al., 2008; Kriegstein and Alvarez-Buylla, 2009).”

“…have shown that functional compensation commonly occurs during development when the gene is constitutively deleted but not when the protein is acutely lost or inhibited (Deuel et al., 2006; Koizumi et al., 2006; Fasano et al., 2007; Satyanarayana and cortical neurogenesis than at later stages.”

“In particular, FMRP was recently shown to play an important role in the proliferation of neural stem cells in the Drosophila larval brain (Callan et al., 2010) and in the adult mouse brain (Luo et al., 2010).”

“Nonetheless, we found that the H119E mutation, which specifically impairs the actin-binding activity of Pfn1 (Suetsugu et al., 1998), abolished the rescue of RGC depletion by Pfn1 (Fig.”

“For instance, the genetic interaction between dFmr1 and dRac1 (Lee et al., 2003; Schenck et al., 2003) and that between dFmr1 and aPKC (Zarnescu et al., 2005) are either antagonistic or synergistic, depending on the cellular contexts.”

“In neocortical neural stem cells, F-actin forms a distinct ring-like structure at the apical endfeet (Chenn et al., 1998).”

“Magnetic resonance imaging analysis of FXS patients has revealed widespread bidirectional brain volume changes (Gothelf et al., 2008).”

“This explanation would be consistent with the previous observation that FMRP deficiency leads to increased neuronal production in cultured neurospheres (Castrén et al., 2005).”

“In Drosophila, dFmr1 (ortholog of FMRP) genetically interacts with profilin (Reeve et al., 2005), a core actin-regulatory protein that promotes F-actin formation (Birbach, 2008).”

“Furthermore, analysis of skeletal and cardiac muscles in Fxr1 knock-out mouse embryos has revealed actin defects in these tissues (Mientjes et al., 2004).”

“The I304N mutation impairs the association of FMRP with RNA (Bassell and Warren, 2008) and renders the protein a null mutant (Zang et al., 2009).”

“Behavioral analysis of Fmr1 Fxr2 double knock-out mice suggests that the loss of FMRP may be partially compensated for by FXR2 (Spencer et al., 2006), although the mechanism of compensation remains unclear.”

“5 (Miyama et al., 1997).”

“In Drosophila, dFmr1 (ortholog of FMRP) genetically interacts with profilin (Reeve et al., 2005), a core actin-regulatory protein that promotes F-actin formation (Birbach, 2008).”

“Although a previous study (Tervonen et al., 2009) observed normal expression of cytoplasmic markers of RGCs in Fmr1 knock-out mouse embryos during late neocortical neurogenesis, a possible change in RGC numbers during earlier stages of neocortical neurogenesis cannot be ruled out.”

“In particular, FMRP was recently shown to play an important role in the proliferation of neural stem cells in the Drosophila larval brain (Callan et al., 2010) and in the adult mouse brain (Luo et al., 2010).”

“, 2003) and that between dFmr1 and aPKC (Zarnescu et al., 2005) are either antagonistic or synergistic, depending on the cellular contexts.”

“The in utero electroporation procedure was performed as described by Walantus et al. (2007) with modifications.”

“…loss of Fmr1 has been associated with abnormalities in cortical development and dendritic spine formation, which may contribute to aberrant learning and behavior in fragile X syndrome (Castrén et al., 2005; La Fata et al., 2014; Saffary and Xie, 2011; Shen et al., 2019; Tervonen et al., 2009).”