
DOI . ORG {
}
Title[redir]:
The Tlx Gene Regulates the Timing of Neurogenesis in the Cortex | Journal of Neuroscience
Description:
The tailless ( tlx ) gene is a forebrain-restricted transcription factor. Tlx mutant animals exhibit a reduction in the size of the cerebral hemispheres and associated structures ([Monaghan et al., 1997][1]). Superficial cortical layers are specifically reduced, whereas deep layers are relatively unaltered ([Land and Monaghan, 2003][2]). To determine whether the adult laminar phenotype has a developmental etiology and whether it is associated with a change in proliferation/differentiation decisions, we examined the cell cycle and neurogenesis in the embryonic cortex. We found that there is a temporal and regional requirement for the Tlx protein in progenitor cells (PCs). Neurons prematurely differentiate at all rostrocaudal levels up to mid-neurogenesis in mutant animals. Heterozygote animals have an intermediate phenotype indicating there is a threshold requirement for Tlx in early cortical neurogenesis. Our studies indicate that PCs in the ventricular zone are sensitive to loss of Tlx in caudal regions only; however, PCs in the subventricular zone are altered at all rostrocaudal levels in tlx -deficient animals. Furthermore, we found that the cell cycle is shorter from embryonic day 9.5 in tlx – / – embryos. At mid-neurogenesis, the PC population becomes depleted, and late PCs have a longer cell cycle in tlx-deficient animals. Consequently, later generated structures, such as upper cortical layers, the dentate gyrus, and the olfactory bulbs, are severely reduced. These studies indicate that tlx is an essential intrinsic regulator in the decision to proliferate or differentiate in the developing forebrain. [1]: #ref-30 [2]: #ref-22
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Keywords {🔍}
cells, tlx, cell, animals, number, mutant, pcs, cycle, scholar, wildtype, caudal, svz, cortical, regions, cortex, cerebral, brdu, fig, layers, compared, tlxdeficient, dorsal, reduced, telencephalon, observed, embryos, early, rostral, levels, intermediate, sections, labeled, full, neurogenesis, neurons, development, time, textgoogle, openurlabstractfree, monaghan, size, loss, studies, developing, proliferation, littermates, table, examined, fraction, wall,
Topics {✒️}
neural helix-loop-helix factors anti-brdu antibody [mouse-α-brdu brdu-positive/tuj1-positive cells forebrain-restricted transcription factor dapi-positive/brdu-negative nuclei short-term brdu pulses exhibited lighter/punctate staining 150-μm-wide window encompassing phosphohistone h3-positive cells brdu-positive/tuj1-negative laminar-specific deficits result long-term brdu studies short-term brdu studies cr-positive cells lined short-term brdu experiments tuj1 double-positive cells fluorescent brdu-positive cells map2-positive cells lined entire brdu-labeled population gray bars represent discontinuous single-cell layer tlx-deficient pcs divide 50 μg/gm bromodeoxyuridine authors editorial board directly regulate proliferation/differentiation main content log white bars represent issue journal jneurosci editorial board boundary parallel-oriented cells cr-positive cell number o'leary dd terminal neuronal differentiation cajal-retzius cell short-term brdu animals received injections tlx-deficient animals compared southern biotechnology research mammalian neuronal differentiation rat-α-brdu black line represents cajal-retzius cells cy2 secondary antibody brdu incorporation include phosphohistone h3 staining wild-type animals examined long-lasting consequences phosphohistone-positive cells phosphohistone h3 labeling neural stem cells
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