Article

Tangential Neuronal Migration Controls Axon Guidance: A Role for Neuregulin-1 in Thalamocortical Axon Navigation

Instituto de Neurociencias de Alicante, CSIC & Universidad Miguel Hernández, 03550 Sant Joan d'Alacant, Spain.
Cell (Impact Factor: 33.12). 05/2006; 125(1):127-42. DOI: 10.1016/j.cell.2006.01.042
Source: PubMed

ABSTRACT Neuronal migration and axon guidance constitute fundamental processes in brain development that are generally studied independently. Although both share common mechanisms of cell biology and biochemistry, little is known about their coordinated integration in the formation of neural circuits. Here we show that the development of the thalamocortical projection, one of the most prominent tracts in the mammalian brain, depends on the early tangential migration of a population of neurons derived from the ventral telencephalon. This tangential migration contributes to the establishment of a permissive corridor that is essential for thalamocortical axon pathfinding. Our results also demonstrate that in this process two different products of the Neuregulin-1 gene, CRD-NRG1 and Ig-NRG1, mediate the guidance of thalamocortical axons. These results show that neuronal tangential migration constitutes a novel mechanism to control the timely arrangement of guidance cues required for axonal tract formation in the mammalian brain.

Download full-text

Full-text

Available from: David A Talmage, Sep 05, 2015
1 Follower
 · 
116 Views
 · 
97 Downloads
  • Source
    • "In parallel, guidepost cells localized along the path have been proposed to extend projections that guide TCAs (Fig. 2A) [11,12,14,23,25–28]: for instance in the perireticular region [29], in the striatal region [28,30–32] and nearby the PSB [11] [12] [33]. In addition, tangential migration allows the formation of another guidepost permissive corridor required for TCAs pathfinding through the subpallium (Fig. 2A) [24] [34]. Indeed, an abnormal formation of the corridor leads to a defective TCAs pathway [34] [35] [36]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sensory perception relies on the formation of stereotyped maps inside the brain. This feature is particularly well illustrated in the mammalian neocortex, which is subdivided in distinct cortical sensory areas that comprise topological maps, such as the somatosensory homunculus in human or the barrel field of the large whiskers in rodents. How somatosensory maps are formed and relayed into the neocortex remain essential questions in developmental neuroscience. Here, we will present our current knowledge on whisker map transfer in the mouse model, with the goal of linking embryonic and postnatal studies into a comprehensive framework.
    Seminars in Cell and Developmental Biology 11/2014; 35. DOI:10.1016/j.semcdb.2014.07.005 · 5.97 Impact Factor
  • Source
    • "Mechanistically, prethalamic and telencephalic guidepost cells (Molná r et al., 2012) may be the critical sources of Linx that promote extension of thalamocortical axons en route to the neocortex. Thalamic axon guidance cues, which include slits, netrin-1, neuregulin-1, ephrins, EphB1/2, Sema3A, and Sema3F (Demyanenko et al., 2011; Dufour et al., 2003; Ló pez-Bendito et al., 2006; Mé tin et al., 1997; Robichaux et al., 2014; Wright et al., 2007), may cooperatively function with Linx to establish early thalamocortical projections through the DTB en route to the cortex. Linx may also modulate expression or availability of the thalamic axon guidance cues. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During the development of forebrain connectivity, ascending thalamocortical and descending corticofugal axons first intermingle at the pallial-subpallial boundary to form the internal capsule (IC). However, the identity of molecular cues that guide these axons remains largely unknown. Here, we show that the transmembrane protein Linx is robustly expressed in the prethalamus and lateral ganglionic eminence-derived corridor and on corticofugal axons, but not on thalamocortical axons, and that mice with a null mutation of Linx exhibit a complete absence of the IC. Moreover, regional inactivation of Linx either in the prethalamus and LGE or in the neocortex leads to a failure of IC formation. Furthermore, Linx binds to thalamocortical projections, and it promotes outgrowth of thalamic axons. Thus, Linx guides the extension of thalamocortical axons in the ventral forebrain, and subsequently, it mediates reciprocal interactions between thalamocortical and corticofugal axons to form the IC.
    Neuron 06/2014; 83(1). DOI:10.1016/j.neuron.2014.05.020 · 15.98 Impact Factor
  • Source
    • "Two critical neurodevelopmental genes that have been linked to schizophrenia susceptibility are neuregulin 1 (NRG1) and its receptor ErbB4 (Norton et al., 2006; Silberberg et al., 2006; Stefansson, 2002). NRG1-mediated ErbB4 signalling is implicated in a number of critical neurobiological processes, especially cortical interneuron migration and interneuron differentiation (Anton et al., 2004; del Pino et al., 2013; Fazzari et al., 2010; Flames et al., 2004; Ghashghaei et al., 2006; López-Bendito et al., 2006; Okada and Corfas, 2004; Rio et al., 1997; Tamura et al., 2012). Abnormal NRG1-ErbB4 signalling results in compromised development of the brain circuitry involving GABA (gamma-aminobutyric acid)containing interneurons (Fazzari et al., 2010; Mei and Xiong, 2008; O'Tuathaigh et al., 2007; Stefansson, 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuregulin1 and its receptor ErbB4 are confirmed risk genes for schizophrenia, but the neuropathological alterations in NRG1-ErbB4 in schizophrenia are unclear. The present investigations therefore focused on determining lamina specific (ErbB4-pan) and quantitative (pan, JMa, JMb, CYT1 and CYT2) mRNA changes in the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. We also determined which neuronal profiles are ErbB4 mRNA+ in the human DLPFC and the relationship between ErbB4 and interneuron marker mRNAs. In situ hybridisation and quantitative PCR measurements were performed to determine changes in ErbB4 splice variant mRNA levels in the DLPFC in schizophrenia (n=37) compared to control (n=37) subjects. Cortical neurons expressing ErbB4-pan were labelled with silver grain clusters. Correlations were performed between ErbB4 and interneuron mRNA levels. ErbB4-pan mRNA was significantly increased (layers I-II, V) in the DLPFC in schizophrenia. Silver grain clusters for ErbB4-pan were detected predominantly over small-medium neurons with low-no expression in the larger, paler, more triangular neuronal profiles. ErbB4-JMa mRNA expression was increased in schizophrenia. Somatostatin, neuropeptide Y and vasoactive intestinal peptide mRNAs negatively correlated with ErbB4-JMa mRNA in people with schizophrenia. Our findings demonstrate that ErbB4-pan laminar mRNA expression is elevated (layers I, II, V) in schizophrenia. At the cellular level, ErbB4-pan mRNA+ signal was detected predominantly in interneuron-like neurons. We provide evidence from this independent Australian post-mortem cohort that ErbB4-JMa expression is elevated in schizophrenia and is linked to deficits in dendrite-targeting somatostatin, neuropeptide Y and vasoactive intestinal peptide interneurons.
    Journal of Psychiatric Research 03/2014; In press. DOI:10.1016/j.jpsychires.2014.02.014 · 4.09 Impact Factor
Show more