In JoVE (1)
Articles by Anthony S. LaMantia in JoVE
Isolation of Cerebrospinal Fluid from Rodent Embryos for use with Dissected Cerebral Cortical Explants Mauro W. Zappaterra1, Anthony S. LaMantia2, Christopher A. Walsh3,4, Maria K. Lehtinen5 1Department of Physical Medicine and Rehabilitation, VA Greater Los Angeles Healthcare System, 2Department of Pharmacology and Physiology, Institute for Neuroscience, The George Washington University School of Medicine and Health Sciences, 3Division of Genetics, Department of Medicine, Boston Children's Hospital, 4Howard Hughes Medical Institute, Boston Children's Hospital, 5Department of Pathology, Boston Children's Hospital, Harvard Medical School The ventricular cerebrospinal fluid (CSF) bathes the neuroepithelial and cerebral cortical progenitor cells during early brain development in the embryo. Here we describe the method developed to isolate ventricular CSF from rodent embryos of different ages in order to investigate its biological function. In addition, we demonstrate our cerebral cortical explant dissection and culture technique that allows for explant growth with minimal volumes of culture medium or CSF.
Other articles by Anthony S. LaMantia on PubMed
Recent Advances in the Neurobiology of Schizophrenia Molecular Interventions. Feb, 2003 | Pubmed ID: 14993436 Despite great progress in basic schizophrenia research, the conclusive identification of specific etiological factors or pathogenic processes in the illness has remained elusive. The convergence of modern neuroscientific studies in molecular genetics, molecular neuropathology, neurophysiology, in vivo brain imaging, and psychopharmacology, however, indicates that we may be coming much closer to understanding the molecular basis of schizophrenia. Schizophrenia may be a neurodevelopmental and progressive disorder with multiple biochemical abnormalities involving the dopaminergic, serotonin, glutamate, and gamma -aminobutyric acidergic systems. In the near future, biological markers for the illness may come from the combination of diverse assessment techniques. An understanding of the pathophysiology of schizophrenia will be essential to the discovery of preventive measures and therapeutic intervention. Rapidly advancing research into schizophrenia includes diverse etiological hypotheses, and offers directions for future research and treatments.
The Apical Complex Couples Cell Fate and Cell Survival to Cerebral Cortical Development Neuron. Apr, 2010 | Pubmed ID: 20399730 Cortical development depends upon tightly controlled cell fate and cell survival decisions that generate a functional neuronal population, but the coordination of these two processes is poorly understood. Here we show that conditional removal of a key apical complex protein, Pals1, causes premature withdrawal from the cell cycle, inducing excessive generation of early-born postmitotic neurons followed by surprisingly massive and rapid cell death, leading to the abrogation of virtually the entire cortical structure. Pals1 loss shows exquisite dosage sensitivity, so that heterozygote mutants show an intermediate phenotype on cell fate and cell death. Loss of Pals1 blocks essential cell survival signals, including the mammalian target of rapamycin (mTOR) pathway, while mTORC1 activation partially rescues Pals1 deficiency. These data highlight unexpected roles of the apical complex protein Pals1 in cell survival through interactions with mTOR signaling.
The Cerebrospinal Fluid Provides a Proliferative Niche for Neural Progenitor Cells Neuron. Mar, 2011 | Pubmed ID: 21382550 Cortical development depends on the active integration of cell-autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions.