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 Developmental Neuroscience
How does the brain develop? In the beginning there are just a few cells. Then comes proliferation, as cells grow and divide ... and differentiation, as cells become specific types with specific properties ... and migrate to the appropriate location ... and the cell type called neurons grow axons to make the right synaptic connections. What emerges is a brain with a precise structure and intricate circuitry.
Understanding the developmental process isn't just a matter of understanding the genome; most cells in the body have the same genes, yet differentiate into vastly different cell types, composing structurally and functionally distinct organs (like the brain). Development is a process of spatial and temporal gene expression.
All organs of the body have anatomical structure which emerges during development; but in addition, brain cells called neurons make thousands of synaptic interconnections as the brain forms and develops. These connections are often quite specific -- neurons process and transfer information along highly circumscribed pathways -- so this leads to another interesting question in developmental neuroscience: how do neurons find the appropriate synaptic targets?
Perhaps surprisingly, the initial development of the nervous system doesn't produce exactly the desired number of neurons, but evidently it produces many more than is needed. The result is neuronal cell death, which removes a considerable proportion of neurons and "sculpts" functioning circuits. Which neurons survive or not is a subject of much research; some of the important factors seem to be electrical activity, uptake of growth factor substances, and genetic "programming".
Labs at Penn that
have developmental neuroscience projects:
William Armstead, PhD Control of cerebral hemodynamics during physiologic and pathologic conditions such as traumatic brain injury and cerebral ischemia/reperfusion.
Rita Balice-Gordon, PhD
Activity-dependent synaptic plasticity during neural development, using
neuromuscular and cns synapses as model systems; neurotrophic and other
cell-cell signaling mechanisms underlying synapse formation and maintenance.
Cluster of dye-coupled motor neurons from a P1 rat spinal cord. After
injection of Neurobiotin, a low molecular mass tracer known to cross
gap junction channels, into a single identified lumbar motor neuron,
several labeled motor neurons were found in spinal cord sections after
staining with fluorescein-conjugated strepavidin. Cluster size decreases
during the first week of life; in adult animals, only single motor neurons
are found labeled after a similar injection.
Greg Bashaw, PhD Molecular
mechanisms of axon growth and guidance during nervous system development.
We are interested specifically in how axon guidance receptors specify
attractive and repulsive signals and transmit these signals to the navigating
growth cone to generate a directed motile response.
Amy Brooks-Kayal, MD Developmental and Molecular Neuroscience, Epilepsy
Bryan Crenshaw, PhD
Analysis of the role of transcription factors during nervous system
development. Embryonic transgenic mouse demonstrating the expression
pattern of the neural enhancer elements in the POU-domain gene, Brn4/Pou3f4.
This early midgestation embryo contains a transgene composed of the
enhancer elements of the Brn4/Pou34 gene driving the expression of a
lacZ reporter gene from a non-specific viral (SV40) promoter. These
data demonstrate that a 2.1 kb enhancer region of the Brn4/Pou3f4 gene
lying between -3.3 and -1.2 kb upstream of the initiator methionine
codon is capable of recapitulating the expression pattern of the endogenous
gene in the neural tube.
Matthew Dalva, PhD Cellular and molecular mechanisms guiding the process of synapse formation between CNS neurons; Roles of activity-dependent and activity-independent cues in cell-cell interaction in synapse development
Joshua Dunaief, MD, PhD Age-related macular degeneration (AMD), oxidative stress in retinal disease, retinal iron metabolism, apoptosis in the retina.
Stephen M. Echteler, PhD Cellular and molecular mechanisms of synapse formation within the developing ear
Jeffrey A. Golden, MD Patterning and Cell Migration in the Developing Nervous System
Michael Granato, PhD Genetic control of axonal guidance in the zebrafish; the zebrafish as a model system for motor behavior regulation in psychiatric diseases
Judith B. Grinspan, PhD Origin and development of oligodendroglia and synthesis of myelin; control of proliferation, differentiation and survival of the oligodendroglial lineage; plasticity of oligodendroglia; programmed cell death in myelinating cells
Daniel S. Kessler, PhD Vertebrate development; signal transduction; transcriptional regulation; primary germ layers; Spemann's organizer Peter S. Klein, MD, PhD Mechanism of lithium action in behavior and development, Wnt signaling in vertebrate embryogenesis and neuronal signal transduction
Peter Le Roux, MD, FACS Dendrites, neurodevelopment, bone morphogenetic proteins, glutamate excitotoxicity, neural regeneration
Kazuko Nishikura, PhD Molecular mechanisms and biological significance of A-to-I RNA editing
Brenda Porter, MD, PhD
I am interested in understanding the cellular and molecular changes
that contribute to the development of epilepsy in the immature brain
Jonathan A. Raper, PhD Developmental neurobiology; growth cone guidance; cell recognition; cell motility; and regeneration
A retinal growth cone loses its normal motile structure and is paralyzed
when it touches a sympathetic axon in culture
Teresa Reyes, PhD Dept of Pharmacology: Central nervous system circuitry controlling food intake and metabolism; illness and infection associated anorexia and cachexia; development of obesity and metabolic syndrome in response to in utero programming (maternal and fetal undernutrition, stress or infection)
Jean-Pierre Saint-Jeannet, PhD Regulation of cell diversity in the developing spinal cord
James C. Saunders, PhD Psychobiology and neurobiology of hearing
Steve Scherer, MD/PhD Axon-Schwann cell interactions in developing and regenerating nerves
Michael E. Selzer, MD/PhD Spinal cord regeneration in lamprey
Albert J. Stunkard, MD Genetic, psychological, therapeutic and developmental studies of human obesity and eating disorders
Steven A. Thomas, MD/PhD The roles of neurotransmission in development, neurophysiology and ultimately behavior
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