191 research outputs found
EMX2 regulates sizes and positioning of the primary sensory and motor areas in neocortex by direct specification of cortical progenitors
Genetic studies of neocortical area patterning are limited, because mice deficient for candidate regulatory genes die before areas emerge and have other compli-cating issues. To define roles for the homeodomain transcription factor EMX2, we engineered nestin-Emx2 transgenic mice that overexpress Emx2 in cortical pro-genitors coincident with expression of endogenous Emx2 and survive postnatally. Cortical size, lamina-tion, thalamus, and thalamocortical pathfinding are normal in homozygous nestin-Emx2 mice. However, primary sensory and motor areas are disproportion-ately altered in size and shift rostrolaterally. Heterozygous transgenics have similar but smaller changes. Opposite changes are found in heterozygous Emx2 knockout mice. Fgf8 expression in the commissural plate of nestin-Emx2 mice is indistinguishable from wild-type, but Pax6 expression is downregulated in rostral cortical progenitors, suggesting that EMX2 re-pression of PAX6 specification of rostral identities contributes to reduced rostral areas. We conclude that EMX2 levels in cortical progenitors disproportionately specify sizes and positions of primary cortical areas
Slits Are Chemorepellents Endogenous to Hypothalamus and Steer Thalamocortical Axons into Ventral Telencephalon
Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into ventral telencephalon. During TCA pathfinding, Slit1 and Slit2 are expressed in hypothalamus and ventral thalamus and Robo1 and Robo2 are expressed in dorsal thalamus. In collagen gel cocultures of dorsal thalamus and Slit2-expressing cells, axon number and length are decreased on the explant side facing Slit2-expressing cells, overall axon outgrowth is diminished, and axons turn away from the Slit2-expressing cells. Thus, Slit2 is an inhibitor and chemorepellent for dorsal thalamic axons. Collagen gel cocultures of dorsal thalamus with sections of live diencephalon, with and without the hypothalamus portion overlaid with Robo2-fc-expressing cells to block Slit function, identify Slits as the hypothalamic chemorepellent. Thus, Slits are chemorepellents for TCAs endogenous to hypothalamus and steer TCAs from diencephalon into ventral telencephalon, a critical pathfinding event defective in Slit and Robo2 mutant mice
Effects of dietary Na+ deprivation on epithelial Na+ channel (ENaC), BDNF, and TrkB mRNA expression in the rat tongue
<p>Abstract</p> <p>Background</p> <p>In rodents, dietary Na<sup>+ </sup>deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na<sup>+ </sup>stimulation. However, in the rat taste bud cells Na<sup>+ </sup>deprivation increases the number of amiloride sensitive epithelial Na<sup>+ </sup>channels (ENaC), which are considered as the "receptor" of the Na<sup>+ </sup>component of salt taste. To explore the mechanisms, the expression of the three ENaC subunits (α, β and γ) in taste buds were observed from rats fed with diets containing either 0.03% (Na<sup>+ </sup>deprivation) or 1% (control) NaCl for 15 days, by using <it>in situ </it>hybridization and real-time quantitative RT-PCR (qRT-PCR). Since BDNF/TrkB signaling is involved in the neural innervation of taste buds, the effects of Na<sup>+ </sup>deprivation on BDNF and its receptor TrkB expression in the rat taste buds were also examined.</p> <p>Results</p> <p><it>In situ </it>hybridization analysis showed that all three ENaC subunit mRNAs were found in the rat fungiform taste buds and lingual epithelia, but in the vallate and foliate taste buds, only α ENaC mRNA was easily detected, while β and γ ENaC mRNAs were much less than those in the fungiform taste buds. Between control and low Na<sup>+ </sup>fed animals, the numbers of taste bud cells expressing α, β and γ ENaC subunits were not significantly different in the fungiform, vallate and foliate taste buds, respectively. Similarly, qRT-PCR also indicated that Na<sup>+ </sup>deprivation had no effect on any ENaC subunit expression in the three types of taste buds. However, Na<sup>+ </sup>deprivation reduced BDNF mRNA expression by 50% in the fungiform taste buds, but not in the vallate and foliate taste buds. The expression of TrkB was not different between control and Na<sup>+ </sup>deprived rats, irrespective of the taste papillae type.</p> <p>Conclusion</p> <p>The findings demonstrate that dietary Na<sup>+ </sup>deprivation does not change ENaC mRNA expression in rat taste buds, but reduces BDNF mRNA expression in the fungiform taste buds. Given the roles of BDNF in survival of cells and target innervation, our results suggest that dietary Na<sup>+ </sup>deprivation might lead to a loss of gustatory innervation in the mouse fungiform taste buds.</p
Lamination of the cerebral cortex is disturbed in Gli3 mutant mice
AbstractThe layered organization of the cerebral cortex develops in an inside-out pattern, a process which is controlled by the secreted protein reelin. Here we report on cortical lamination in the Gli3 hypomorphic mouse mutant XtJ/Pdn which lacks the cortical hem, a major source of reelin+ Cajal Retzius cells in the cerebral cortex. Unlike other previously described mouse mutants with hem defects, cortical lamination is disturbed in XtJ/Pdn animals. Surprisingly, these layering defects occur in the presence of reelin+ cells which are probably derived from an expanded Dbx1+ progenitor pool in the mutant. However, while these reelin+ neurons and also Calretinin+ cells are initially evenly distributed over the cortical surface they form clusters later during development suggesting a novel role for Gli3 in maintaining the proper arrangement of these cells in the marginal zone. Moreover, the radial glial network is disturbed in the regions of these clusters. In addition, the differentiation of subplate cells is affected which serve as a framework for developing a properly laminated cortex
Lingual deficits in neurotrophin double knockout mice
Brain-derived neurotrophic factor (BDNF) and Neurotrophin 3 (NT-3) are members of the neurotrophin family and are expressed in the developing and adult tongue papillae. BDNF null-mutated mice exhibit specific impairments related to innervation and development of the gustatory system while NT-3 null mice have deficits in their lingual somatosensory innervation. To further evaluate the functional specificity of these neurotrophins in the peripheral gustatory system, we generated double BDNF/NT-3 knockout mice and compared the phenotype to BDNF −/− and wild-type mice. Taste papillae morphology was severely distorted in BDNF −/− x NT-3 −/− mice compared to single BDNF −/− and wild-type mice. The deficits were found throughout the tongue and all gustatory papillae. There was a significant loss of fungiform papillae and the papillae were smaller in size compared to BDNF −/− and wild-type mice. Circumvallate papillae in the double knockouts were smaller and did not contain any intraepithelial nerve fibers. BDNF −/− x NT-3 −/− mice exhibited additive losses in both somatosensory and gustatory innervation indicating that BDNF and NT-3 exert specific roles in the innervation of the tongue. However, the additional loss of fungiform papillae and taste buds in BDNF −/− x NT-3 −/− mice compared to single BDNF knockout mice indicate a synergistic functional role for both BDNF-dependent gustatory and NT-3-dependent somatosensory innervations in taste bud and taste papillae innervation and development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47465/1/11068_2005_Article_3330.pd
Building sensory receptors on the tongue
Neurotrophins, neurotrophin receptors and sensory neurons are required for the development of lingual sense organs. For example, neurotrophin 3 sustains lingual somatosensory neurons. In the traditional view, sensory axons will terminate where neurotrophin expression is most pronounced. Yet, lingual somatosensory axons characteristically terminate in each filiform papilla and in each somatosensory prominence within a cluster of cells expressing the p75 neurotrophin receptor (p75NTR), rather than terminating among the adjacent cells that secrete neurotrophin 3. The p75NTR on special specialized clusters of epithelial cells may promote axonal arborization in vivo since its over-expression by fibroblasts enhances neurite outgrowth from overlying somatosensory neurons in vitro . Two classical observations have implicated gustatory neurons in the development and maintenance of mammalian taste buds—the early arrival times of embryonic innervation and the loss of taste buds after their denervation in adults. In the modern era more than a dozen experimental studies have used early denervation or neurotrophin gene mutations to evaluate mammalian gustatory organ development. Necessary for taste organ development, brain-derived neurotrophic factor sustains developing gustatory neurons. The cardinal conclusion is readily summarized: taste buds in the palate and tongue are induced by innervation. Taste buds are unstable: the death and birth of taste receptor cells relentlessly remodels synaptic connections. As receptor cells turn over, the sensory code for taste quality is probably stabilized by selective synapse formation between each type of gustatory axon and its matching taste receptor cell. We anticipate important new discoveries of molecular interactions among the epithelium, the underlying mesenchyme and gustatory innervation that build the gustatory papillae, their specialized epithelial cells, and the resulting taste buds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47466/1/11068_2005_Article_3332.pd
Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior
Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia
- …