A5047631726- Neurogenesis and neuroplasticity mechanisms
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Neuroinflammation and Neurodegeneration Mechanisms
- Protein Tyrosine Phosphatases
- Pluripotent Stem Cells Research
- Axon Guidance and Neuronal Signaling
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Olfactory and Sensory Function Studies
- Nerve injury and regeneration
- Galectins and Cancer Biology
- FOXO transcription factor regulation
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Stress Responses and Cortisol
- Genetics, Aging, and Longevity in Model Organisms
- Hedgehog Signaling Pathway Studies
- Cancer-related molecular mechanisms research
- Autophagy in Disease and Therapy
- Tissue Engineering and Regenerative Medicine
- Microtubule and mitosis dynamics
- Signaling Pathways in Disease
- Circular RNAs in diseases
- Single-cell and spatial transcriptomics
Cincinnati Children's Hospital Medical Center
2013-2025
University of Cincinnati Medical Center
2007-2025
University of Cincinnati
2006-2020
Society for Developmental and Behavioral Pediatrics
2017
Johns Hopkins All Children's Hospital
2016
Johns Hopkins University
2016
Children's Medical Center
2014
Laboratoire d’immunologie intégrative du cancer
2013
Predictive Biology (United States)
2011
Institute of Developmental Physiology
2007
Glioblastoma multiforme (GBM) is a life-threatening brain tumor. Accumulating evidence suggests that eradication of glioma stem-like cells (GSCs) in GBM essential to achieve cure. The transcription factor FOXM1 has recently gained attention as master regulator mitotic progression cancer various organs. Here, we demonstrate forms protein complex with the kinase MELK GSCs, leading phosphorylation and activation kinase-dependent manner. This MELK-dependent results subsequent increase regulatory...
We have taken a genetic-based fate-mapping approach to determine the specific contributions of telencephalic progenitors structures that comprise amygdalar fear circuit including central (CA), lateral (LA), and basolateral (BLA) amygdala. Our data indicate in ventral pallium (VP) contribute projection neurons LA BLA but not CA. Rather, CA appears derive, at least part, from located ganglionic eminence (vLGE). Diverse groups interneurons populate these nuclei, as predicted our support notion...
Lactate is used as an energy source by producer cells or shuttled to neighboring and tissues. Both glucose lactate fulfill the bioenergetic demand of neurons, latter imported from astrocytes. The contribution astrocytic neuronal bioenergetics mechanisms production are incompletely understood. Through in vivo 1H magnetic resonance spectroscopy, 13C mass electroencephalographic molecular studies, here we show that sensor AMP activated protein kinase (AMPK) regulates survival a...
Activation of the nuclear factor activated T-cell (NFAT) family transcription factors is associated with changes in gene expression and myocyte function adult cardiac skeletal muscle. However, role NFATs normal embryonic heart development not well characterized. In this report, NFATc3 NFATc4 was examined mice targeted disruption both nfatc3 nfatc4 genes. The nfatc3-/-nfatc4-/- demonstrate lethality after day 10.5 have thin ventricles, pericardial effusion, a reduction ventricular...
Previous studies using dominant-mutant constructs have implicated Rac1 GTPase in neuritogenesis and neuronal migration. However, overexpression of dominant mutants generally blocks Rho–GTPase activity; thus, it may not reveal the specific or physiological functions Rac1. To address this issue, we applied a conditional gene-targeting strategy, Foxg1–Cre mice to delete ventricular zone (VZ) telencephalon Dlx5/6–Cre–IRES (internal ribosomal entry site)–EGFP (enhanced green fluorescent protein)...
Neural stem cells (NSCs) reside in widespread regions along the lateral ventricle and generate diverse olfactory bulb (OB) interneuron subtypes adult mouse brain. Molecular mechanisms underlying their regional diversity, however, are not well understood. Here we show that homeodomain transcription factor Gsx2 plays a crucial role region-specific control of NSCs both persistent injury-induced neurogenesis. In intact brain, is expressed regionally restricted subset promotes activation lineage...
Significance The basal ganglia process cortical information that controls purposeful movements and appropriate behavior via the striatopallidal striatonigral pathways. Despite their importance, little is known about developmental mechanisms control formation of these We show here telencephalic progenitors expressing transcription factor Islet1 give rise to neurons this required for normal development pathway. Moreover, mouse mutants exhibit hyperactivity a paradoxical response...
Mice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of Gsx1 Gsx2 genes. To investigate whether Gsx contributes to Dlx1/2 mutant phenotypes, we made compound loss-of-function mutants. Eliminating function from mutants rescued increased expression Ascl1 Hes5 (Notch signaling mediators) Olig2 (oligodendrogenesis mediator). In addition, Dlx1/2;Gsx2 mutants, like Dlx1/2;Ascl1 exacerbated patterning...
In this report we describe the developmental expression and function of Sp8, a member Sp family zinc finger transcription factors, provide evidence that legless transgene insertional mutant is hypomorphic allele Sp8 gene. expressed during embryogenesis in forming apical ectodermal ridge (AER), restricted regions central nervous system, tail bud. Targeted deletion gene gives striking phenotype, with severe truncation both forelimbs hindlimbs, absent tail, as well defects anterior posterior...
Abstract Background The homeobox gene Gsx2 (formerly Gsh2 ) is known to regulate patterning in the lateral ganglionic eminence (LGE) of embryonic telencephalon. In its absence, closely related Gsx1 (previously as Gsh1 can partially compensate and differentiation ventral telencephalic structures, such striatum. However, cellular molecular mechanisms underlying this compensation remain unclear. Results We show here that mutants expressed only a subset progenitors normally express Gsx2. Based...
In caudal regions of the diencephalon, sonic hedgehog (Shh) is expressed in ventral midline prosomeres 1-3 (p1-p3), which underlie pretectum, thalamus and prethalamus, respectively. Shh also zona limitans intrathalamica (zli), a dorsally projecting spike that forms at p2-p3 boundary. The presence two signaling centers has made it difficult to determine specific roles either one regional patterning neuronal fate specification. To investigate requirement from focal source expression we used...
The homeobox gene Gsx2 has previously been shown to be required for the specification of distinct neuronal subtypes derived from lateral ganglionic eminence (LGE) progenitors at specific embryonic time points. However, its role in subsequent generation oligodendrocytes these remains unclear. We have utilized conditional gain-of-function and loss-of-function approaches order elucidate switch between neurogenesis oligodendrogenesis within ventral telencephalon. In absence expression, an...
The intercalated cells (ITCs) of the amygdala have been shown to be critical regulatory components amygdalar circuits, which control appropriate fear responses. Despite this, molecular processes guiding ITC development remain poorly understood. Here we establish zinc finger transcription factor Tshz1 as a marker ITCs during their migration from dorsal lateral ganglionic eminence through maturity. Using germline and conditional knock-out (cKO) mouse models, show that is required for proper...
Gsx2 is a homeodomain transcription factor critical for development of the ventral telencephalon and hindbrain mouse. Loss function results in severe basal ganglia dysgenesis as well defects nucleus tractus solitarius (nTS) together with respiratory failure at birth. De Mori et al. (2019) reported two patients dystonia that encode distinct recessive GSX2 variants, including missense mutation within (GSX2Q251R). Hence, we modelled homologous (i.e. Gsx2Q252R) mouse our biochemical analysis...
Summary The dorsal horn of the mammalian spinal cord is an exquisite example form serving function. It comprised diverse neuronal populations stacked into laminae, each which receives different circuit connections and plays specialized roles in behavior. An outstanding question how this organization emerges during development from apparently homogeneous pool neural progenitors. Here, we found that neurons are diversified by time, with families related cell types born as temporal cohorts, a...
The protein tyrosine phosphatase Shp2 ( PTPN11 ) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal astroglia cell fate decisions. However, its roles the ventral telencephalon during oligodendrogenesis remain largely unknown. gain-of-function (GOF) mutations are observed Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, neurocognitive abnormalities. To gain insight into requirements...