Thalamocortical axons control the cytoarchitecture of neocortical layers by area-specific supply of secretory proteins (original) (raw)
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Fibroblast Growth Factor 8 Regulates Neocortical Guidance of Area-Specific Thalamic Innervation
Journal of Neuroscience, 2005
Thalamic innervation of each neocortical area is vital to cortical function, but the developmental strategies that guide axons to specific areas remain unclear. We took a new approach to determine the contribution of intracortical cues. The cortical patterning molecule fibroblast growth factor 8 (FGF8) was misexpressed in the cortical primordium to rearrange the area map. Thalamic axons faithfully tracked changes in area position and innervated duplicated somatosensory barrel fields induced by an ectopic source of FGF8, indicating that thalamic axons indeed use intracortical positional information. Because cortical layers are generated in temporal order, FGF8 misexpression at different ages could be used to shift regional identity in the subplate and cortical plate either in or out of register. Thalamic axons showed strikingly different responses in the two different conditions, disclosing sources of positional guidance in both subplate and cortical plate. Unexpectedly, axon trajectories indicated that an individual neocortical layer could provide not only laminar but also area-specific guidance. Our findings demonstrate that thalamocortical axons are directed by sequential, positional cues within the cortex and implicate FGF8 as an indirect regulator of thalamocortical innervation.
Fgf8 controls regional identity in the developing thalamus
Development, 2008
The vertebrate thalamus contains multiple sensory nuclei and serves as a relay station to receive sensory information and project to corresponding cortical areas. During development, the progenitor region of the diencephalon is divided into three parts, p1, p2 (presumptive thalamus) and p3, along its longitudinal axis. Besides the local expression of signaling molecules such as sonic hedgehog (Shh), Wnt proteins and Fgf8, the patterning mechanisms of the thalamic nuclei are largely unknown. Using mouse in utero electroporation to overexpress or inhibit endogenous Fgf8 at the diencephalic p2/p3 border, we revealed that it affected gene expression only in the p2 region without altering overall diencephalic size or the expression of other signaling molecules. We demonstrated that two distinctive populations in p2,which can be distinguished by Ngn2 and Mash1 in early embryonic diencephalon, are controlled by Fgf8 activity in complementary manner. Furthermore, we found that FGF activity ...
Sensory Map Transfer to the Neocortex Relies on Pretarget Ordering of Thalamic Axons
Current Biology, 2013
Sensory maps, such as the representation of mouse facial whiskers, are conveyed throughout the nervous system by topographic axonal projections that preserve neighboring relationships between adjacent neurons . In particular, the map transfer to the neocortex is ensured by thalamocortical axons (TCAs), whose terminals are topographically organized in response to intrinsic cortical signals . However, TCAs already show a topographic order early in development, as they navigate toward their target . Here, we show that this preordering of TCAs is required for the transfer of the whisker map to the neocortex. Using Ebf1 conditional inactivation that specifically perturbs the development of an intermediate target, the basal ganglia, we scrambled TCA topography en route to the neocortex without affecting the thalamus or neocortex. Notably, embryonic somatosensory TCAs were shifted toward the visual cortex and showed a substantial intermixing along their trajectory. Somatosensory TCAs rewired postnatally to reach the somatosensory cortex but failed to form a topographic anatomical or functional map. Our study reveals that sensory map transfer relies not only on positional information in the projecting and target structures but also on preordering of axons along their trajectory, thereby opening novel perspectives on brain wiring.
An early cortical progenitor-specific mechanism regulates thalamocortical innervation
bioRxiv, 2020
The cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but “wait” for several days, entering the cortical plate postnatally. We report that when transcription factor Lhx2 is lost in E11.5 cortical progenitors, which give rise to subplate neurons, thalamocortical afferents display premature, exuberant innervation of the E15.5 cortex. Embryonic mutant subplate neurons are correctly positioned below the cortical plate, but they display an altered transcriptome and immature electrophysiological properties during the waiting period. The sensory thalamus in these cortex-specific Lhx2 mutants displays atrophy, eventually leading to severe deficits in thalamocortical innervation. Strikingly, these phenotypes do not manifest if Lhx2 is lost in postmitotic subplate neurons. These results demonstrate a mechanism operating in subplate progenitors that has profound c...
Thalamus-Derived Molecules Promote Survival and Dendritic Growth of Developing Cortical Neurons
Journal of Neuroscience, 2012
The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening by in situ hybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner.
Non-canonical role for Lpar1-EGFP subplate neurons in early postnatal mouse somatosensory cortex
eLife, 2021
Subplate neurons (SPNs) are thought to play a role in nascent sensory processing in neocortex. To better understand how heterogeneity within this population relates to emergent function, we investigated the synaptic connectivity of Lpar1-EGFP SPNs through the first postnatal week in whisker somatosensory cortex (S1BF). These SPNs comprise of two morphological subtypes: fusiform SPNs with local axons and pyramidal SPNs with axons that extend through the marginal zone. The former receive translaminar synaptic input up until the emergence of the whisker barrels, a timepoint coincident with significant cell death. In contrast, pyramidal SPNs receive local input from the subplate at early ages but then – during the later time window – acquire input from overlying cortex. Combined electrical and optogenetic activation of thalamic afferents identified that Lpar1-EGFP SPNs receive sparse thalamic innervation. These data reveal components of the postnatal network that interpret sparse thalam...
Region-specific gene expression in early postnatal mouse thalamus
The Journal of Comparative Neurology, 2011
Previous studies in the developing mouse thalamus have demonstrated that regional identity is established during early stages of development (Suzuki-Hirano et al. J. Comp. Neurol. 2011;519:528-543). However, the developing thalamus often shows little resemblance to the anatomical organization of the postnatal thalamus, making it difficult to identify genes that might mediate the organization of thalamic nuclei. We therefore analyzed the expression pattern of genes that we have identified as showing regional expression in embryonic thalamus on postnatal days (P) 6-8 by using in situ hybridization. We also identified several genes expressed only in the postnatal thalamus with restricted expression in specific nuclei. We first demonstrated the selective expression of neurotransmitter-related genes (vGlut2, vGAT, D2R, and HTR2C), identifying the neurotransmitter subtypes of cells in this region, and we also demonstrated selective expression of additional genes in the thalamus (Steel,
Journal of Neuroscience, 2010
The embryonic diencephalon gives rise to the vertebrate thalamus and hypothalamus, which play essential roles in sensory information processing and control of physiological homeostasis and behavior, respectively. In this review, we present new steps toward characterizing the molecular pathways that control development of these structures, based on findings in a variety of model organisms. We highlight advances in understanding how early regional patterning is orchestrated through the action of secreted signaling molecules such as Sonic hedgehog and fibroblast growth factors. We address the role of individual transcription factors in control of the regional identity and neural differentiation within the developing diencephalon, emphasizing the contribution of recent large-scale gene expression studies in providing an extensive catalog of candidate regulators of hypothalamic neural cell fate specification. Finally, we evaluate the molecular mechanisms involved in the experience-dependent development of both thalamo-cortical and hypothalamic neural circuitry.
Developmental biology, 2007
Fibroblast growth factors (FGF) receptors FgfR1, FgfR2 and FgfR3 are differentially regulated during oligodendrocyte (OL) maturation in vitro: FgfR3 is expressed by OL progenitors whereas FgfR2 is expressed by differentiated OLs [Mol Cell Neurosci 1996;7:263-275], and we have recently shown that FgfR3 is required for the timely differentiation of OLs in vivo [J Neurosci 2003;23:883-894]. Here we have used in situ hybridization to investigate the expression patterns of FgfR1-3 and compare them to the putative OL progenitor markers Olig2, Pdgfr· and Plp/dm20 as a function of development in vivo, in particular at sites of OL specification, migration or differentiation in the mouse forebrain and cerebellum. We show that at early stages FgfR1-3 expression overlaps with that of Olig2 in the embryonic ventricular zone of the lateral and medial ganglionic eminences. Further, a scattered population of cells expressing FgfR3 (but not FgfR1 or FgfR2) in the ventral telencephalon appear to arise from the ventricular zone, and at later stages are found more dorsally in the cortex, in an overall pattern similar to Olig2 and/or Pdgfr·. Postnatal expression of FgfR2 increases with age, more prominently in specific regions, including the cortical and cerebellar white matter and optic nerve. Thus, the differential expression pattern of FgfR2 and FgfR3 observed in vivo suggests that their expression is developmentally regulated in a manner consistent with the pattern of their expression in culture. These data provide further insights into role of FgfRs in OL development, and they emphasize that these receptors are positioned both spatially and temporally to impact OL generation in vivo.