Flora M. Vaccarino. M.D.
M.D. 1979, Padua University Medical School
Associate Professor
Child Study Center
& Section of Neurobiology
230 South Frontage Road
New Haven CT
USA 06520
SHM, I-373
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Research
The principal goal of my research is to understand the mechanisms that control neuron number in cortical systems related to the categorization of sensorimotor input. We are exploring the interactions between a class of growth factors called Fibroblast growth Factors (FGF) and Otx1, a homeodomain gene that controls the development of the dorsal neocortex, particularly fronto-parietal areas.
Regulation of cell number during cerebral cortical development.We have shown that a ligand of the Fibroblast Growth Factor family, FGF2, nearly doubles the number of cerebral cortical neurons generated during embryogenesis when injected in the embryonic rat brain ventricles (Vaccarino et al, 1999). FGF2 is sufficient to increase the size of the cortical progenitor pool both in vitro and in vivo (Vaccarino et al, 1995 and 1999), and is also required for normal neurogenesis in the murine cerebral cortex (Raballo et al, 2000). In the absence of FGF2, a large portion of cortical progenitor cells is missing and cortical neurogenesis is decreased.
The lack of FGF2 affects the generation of specific neuronal types more concentrated in anterior sensorimotor cortical areas. This may be due to a specific interaction of FGF2 with homeodomain nuclear transcription factors of the Emx and Otx families (Robel et al, 1995). To study the role of FGF receptors in brain development, we have generated transgenic mice carrying dominant negative FGF receptors throughout the dorsal telencephalon.
Developmental abnormalities of the telencephalon in neuropsychiatric disorders. Cortical neuron number is decreased in schizophrenia, in some forms of autism and in many forms of mental retardation. The volume of the basal ganglia is decreased in Tourette's syndrome. In addition to genetic factors, environmental noxae during brain development may affect cell number by altering cell growth or cell death. We are conducting a stereological analysis of post-mortem human brains to assess the number of neurons within defined brain areas in specific neuropsychiatric disorders. Furthermore, we are attempting to model such neuropathological alterations in rodents exposed to hypoxia at different stages of development. We envision that the brain responds to perinatal stress by the reactivation of programs that regulate cell generation and survival at earlier stages of development.
Last modified: August 15, 2000. (KP)
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