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One or more keywords matched the following properties of Grove, Elizabeth
keywords Embryonic Pattern Formation
overview Determining the mechanisms of cerebral cortical development is essential to understanding the functions, disorders, and evolution of the brain. My research focuses on the embryonic and early postnatal development of cerebral cortex in the mouse. Specific questions include: how part of the embryonic neuroepithelium is divided, or “patterned” into the neocortex and hippocampus; how different hippocampal neuronal cell types are specified; and how a consistent map of functionally distinct areas is laid out in neocortex. To a developmental biologist the cerebral cortex may seem too complex a system for studies of tissue patterning and cell type specification. My lab, however, has contributed to a model in which the embryonic cortex is initially patterned by secreted signaling molecules, including Fibroblast Growth Factor (FGF) 8, and the Wnt protein, Wnt3a, together with downstream transcription factors, in much the same way as in the rest of the embryo. FGF8 disperses from an anterior source to establish the anterior to posterior (A/P) axis of the neocortical area map. Wnt3a influences the medial to lateral (M/L) axis and is also required for development of the hippocampus. Together, FGF8 and Wnt3a shape expression gradients of transcription factor genes that control the size and position of neocortical areas as well as hippocampal growth. This model is still incomplete. For example, how sharp area boundaries arise from graded gene expression is unclear. Classically, for this step, a mechanism specific to the nervous system is proposed, namely the growth of axons from the thalamus into the neocortex. Yet previous findings indicate that precise guidance cues lie within nascent neocortical areas. To identify area-specific axon guidance molecules, we plan to harvest in cells from a mouse in which sensory areas are marked by green fluorescence, and compare the transcriptomes of different areas using RNA-Seq. A major outstanding task is to determine if our model of cortical patterning, based on studies of the mouse, holds for larger, multi-folded (gyrencephalic) brains of carnivores and primates. Common features of the area map, conserved across mammals, suggest the model could generalize, and early evidence from a study of the gyrencephalic ferret supports this hypothesis. Methods: Candidate genes are identified and their function altered using mouse genetics and a fine-scale method of in utero microelectroporation that we pioneered. The cortical phenotype of mice in which gene function is altered is analyzed by area-specific gene and protein expression and connectivity, and occasionally by behavior. We discovered, for instance, that part of the hippocampus is shrunken in mice deficient in BMP signaling, and that these mice were "fearless" in situations that would normally induce anxiety, supporting a new view of hippocampal function. Cell type specific transcriptomes will be identified with single cell RNA-Seq.
One or more keywords matched the following items that are connected to Grove, Elizabeth
Item TypeName
Concept Body Patterning
Academic Article Dorsoventral patterning of the telencephalon is disrupted in the mouse mutant extra-toes(J).
Academic Article Neocortex patterning by the secreted signaling molecule FGF8.
Academic Article Patterning events and specification signals in the developing hippocampus.
Academic Article Patterning the mammalian cerebral cortex.
Academic Article Detailed field pattern is intrinsic to the embryonic mouse hippocampus early in neurogenesis.
Academic Article The telencephalon saved by TLC.
Academic Article Conserved expression of Hoxa1 in neurons at the ventral forebrain/midbrain boundary of vertebrates.
Academic Article Neuronal precursor cells in the rat hippocampal formation contribute to more than one cytoarchitectonic area.
Academic Article LIM-homeodomain gene Lhx2 regulates the formation of the cortical hem.
Academic Article Wnt genes define distinct boundaries in the developing human brain: implications for human forebrain patterning.
Academic Article Patterning the dorsal telencephalon: a role for sonic hedgehog?
Academic Article The derivatives of the Wnt3a lineage in the central nervous system.
Academic Article Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex.
Academic Article Patterning the developing cerebral cortex.
Academic Article Area and layer patterning in the developing cerebral cortex.
Academic Article FGF8 acts as a classic diffusible morphogen to pattern the neocortex.
Academic Article Neuroscience. Organizing the source of memory.
Academic Article Shh and Gli3 regulate formation of the telencephalic-diencephalic junction and suppress an isthmus-like signaling source in the forebrain.
Academic Article Bone morphogenetic protein signaling in the developing telencephalon controls formation of the hippocampal dentate gyrus and modifies fear-related behavior.
Academic Article Emx2 patterns the neocortex by regulating FGF positional signaling.
Academic Article Generating the cerebral cortical area map.
Academic Article Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections.
Academic Article The cortical hem regulates the size and patterning of neocortex.
Academic Article DMRT5 Together with DMRT3 Directly Controls Hippocampus Development and Neocortical Area Map Formation.
Grant Molecular Mechanisms of Cerebral Cortical Patterning
Grant Role Of The Cortical Hem In Patterning The Telencephalon
Grant Molecular Mechanisms of Cerebral Cortical Patterning
Grant Specifying the Neocortical Area Map in the Ferret
Academic Article A model of neocortical area patterning in the lissencephalic mouse may hold for larger gyrencephalic brains.
Grant Development of the neocortical area map
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  • Pattern
  • Formation