<i>Cux‐1</i> and <i>Cux‐2</i> control the development of Reelin expressing cortical interneurons

Cubelos, Beatriz; Sebastián-Serrano, Álvaro; Kim, Seonhee; Redondo, Juan Miguel; Walsh, Christopher A.; Nieto, Marta

doi:10.1002/dneu.20626

Cited by 49 publications

(48 citation statements)

References 21 publications

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“…4(G,N)]. In contrast, the distribution of Brn1, a transcription factor expressed by glutamatergic neurons of layers II-V (McEvilly et al, 2002;Sugitani et al, 2002), and Cux1, a marker for upper layer cortical neurons (Cubelos et al, 2008), revealed a decrease in the density of the upper layers and an increase in Cux1 and Brn1 positive cells in the lower layers of the Bmp7 null cortex as compared with wt [ Fig. 4(E,F,L,M)].…”

Section: Bmp7 Is Required For Proper CC Formationmentioning

confidence: 88%

Appropriate Bmp7 levels are required for the differentiation of midline guidepost cells involved in corpus callosum formation

Sánchez-Camacho

Ortega

Ocaña

et al. 2011

Developmental Neurobiology

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Guidepost cells are essential structures for the establishment of major axonal tracts. How these structures are specified and acquire their axon guidance properties is still poorly understood. Here, we show that in mouse embryos appropriate levels of Bone Morphogenetic Protein 7 (Bmp7), a member of the TGF-β superfamily of secreted proteins, are required for the correct development of the glial wedge, the indusium griseum, and the subcallosal sling, three groups of cells that act as guidepost cells for growing callosal axons. Bmp7 is expressed in the region occupied by these structures and its genetic inactivation in mouse embryos caused a marked reduction and disorganization of these cell populations. On the contrary, infusion of recombinant Bmp7 in the developing forebrain induced their premature differentiation. In both cases, changes were associated with the disruption of callosal axon growth and, in most animals fibers did not cross the midline forming typical Probst bundles. Addition of Bmp7 to cortical explants did not modify the extent of their outgrowth nor their directionality, when explants were exposed to a focalized source of the protein. Together, these results indicate that Bmp7 is indirectly required for corpus callosum formation by controlling the timely differentiation of its guidepost cells.

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Section: Bmp7 Is Required For Proper CC Formationmentioning

confidence: 88%

Appropriate Bmp7 levels are required for the differentiation of midline guidepost cells involved in corpus callosum formation

Sánchez-Camacho

Ortega

Ocaña

et al. 2011

Developmental Neurobiology

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“…4I). These genes include Cux2 and Lhx6, transcription factors previously shown to regulate interneuron migration and differentiation (26,30,32,33). Gad2 (Gad65), which encodes one of the key synthetic enzymes for the predominant cortical interneuron neurotransmitter GABA (34), is also diminished.…”

Section: Altered Interneuron Migration and Motility In The Embryonic mentioning

confidence: 99%

Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome

Meechan

Tucker

Maynard

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Interneurons are thought to be a primary pathogenic target for several behavioral disorders that arise during development, including schizophrenia and autism. It is not known, however, whether genetic lesions associated with these diseases disrupt established molecular mechanisms of interneuron development. We found that diminished 22q11.2 gene dosage-the primary genetic lesion in 22q11.2 deletion syndrome (22q11.2 DS)-specifically compromises the distribution of early-generated parvalbumin-expressing interneurons in the Large Deletion (LgDel) 22q11.2DS mouse model. This change reflects cellautonomous disruption of interneuron migration caused by altered expression of the cytokine C-X-C chemokine receptor type 4 (Cxcr4), an established regulator of this process. Cxcr4 is specifically reduced in LgDel migrating interneurons, and genetic analysis confirms that diminished Cxcr4 alters interneuron migration in LgDel mice. Thus, diminished 22q11.2 gene dosage disrupts cortical circuit development by modifying a critical molecular signaling pathway via Cxcr4 that regulates cortical interneuron migration and placement.

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“…Similar to other extracellular signaling molecules, a critical locus of reelin signaling regulation is at the level of transcription (Erbel-Sieler et al, 2004; Wang et al, 2004; Chen et al, 2007; Miller and Sweatt, 2007; Cubelos et al, 2008), although receptor availability (Duit et al, 2010; Hong et al, 2010; Balmaceda et al, 2014) and secretion (Duveau et al, 2011) may also play a role. However, these mechanisms only serve to adjust the level of reelin signaling, as they are not sufficient to initiate the reelin signal by themselves.…”

Section: Introductionmentioning

confidence: 99%

Extracellular proteolysis of reelin by tissue plasminogen activator following synaptic potentiation

Trotter

Lussier

et al. 2014

Neuroscience

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The secreted glycoprotein reelin plays an indispensable role in neuronal migration during development and in regulating adult synaptic functions. The upstream mechanisms responsible for initiating and regulating the duration and magnitude of reelin signaling are largely unknown. Here we report that reelin is cleaved between EGF-like repeats 6–7 (R6–7) by tissue plasminogen activator (tPA) under cell-free conditions. No changes were detected in the level of reelin and its fragments in the brains of tPA knockouts, implying that other unknown proteases are responsible for generating reelin fragments found constitutively in the adult brain. Induction of NMDAR-independent long-term potentiation with the potassium channel blocker tetraethylammonium chloride (TEA-Cl) led to a specific up-regulation of reelin processing at R6–7 in wild-type mice. In contrast, no changes in reelin expression and processing were observed in tPA knockouts following TEA-Cl treatment. These results demonstrate that synaptic potentiation results in tPA-dependent reelin processing and suggest that extracellular proteolysis of reelin may regulate reelin signaling in the adult brain.

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Cux‐1 and Cux‐2 control the development of Reelin expressing cortical interneurons

Cited by 49 publications

References 21 publications

Appropriate Bmp7 levels are required for the differentiation of midline guidepost cells involved in corpus callosum formation

Appropriate Bmp7 levels are required for the differentiation of midline guidepost cells involved in corpus callosum formation

Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome

Extracellular proteolysis of reelin by tissue plasminogen activator following synaptic potentiation

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