The goal of the Laboratory of Developmental Neurobiology is to understand the molecular and cellular mechanisms underlying the regulation of development and function of the nervous system. Major topics of interest include the mechanisms of processing, intracellular trafficking, and secretion of neuropeptides and hormones; the molecular machinery of secretory vesicle biogenesis and the presynaptic release process; circadian biology with emphasis on the pineal gland and synthesis of melatonin; the coupling between action potentials, neurotransmitters, neurohormones, neurotrophic factors, and the regulation of gene expression. The laboratory carries out its investigations with a variety of cellular systems as well as with knock-out and transgenic animal models. Researchers use wide-ranging analytical techniques that include gene chips, imaging, immunohistochemistry, electron microscopy, and behavioral testing to examine neuronal cell biology, activity-dependent neural and neuromuscular plasticity, and the effects of neurotrophic factors on fetal nervous system development.

Advances include work from Peng Loh’s group, which discovered a master molecule, chromogranin A, that regulates secretory granule biogenesis at the transcriptional and post-translational level and hence neurotransmitter secretion from neuroendocrine cells. Her group has also elucidated the molecular basis for the intracellular missorting of mutant proinsulins in hyperproinsulinemia patients that leads to diabetes. David Klein’s group has established an important element, the binding protein 14-3-3, that regulates the level of the enzyme serotonin N-acetyltransferase that is responsible for the melatonin rhythm-generating system. Andres Buonanno’s group has discovered a new transcription factor, General Transcription Factor 3 (GTF3), that is expressed in numerous tissues, including muscle and brain, and contributes to the establishment of fiber types during perinatal development. The genes encoding GTF3 and its related homolog GTF2i are deleted in individuals with Williams syndrome (WS) who manifest numerous cognitive deficits as well as myotonias. The group’s recent studies using ectopically transfected GTF3 constructs in adult muscles and GFT3-knock-out mice support a role for GTF3 in regulating muscle contractile properties that could be related to the myopathies observed in WS. Phillip Nelson’s group has shown that the ras-mitogen–activated protein kinase (MAPK) and cAMP/PKA-mediated pathways play important roles in neuronal plasticity and Hebbian synapse modulation at the neuromuscular junction. Douglas Brenneman’s group has characterized ADNF, a glial-derived factor involved in the control of neuronal survival, as a multi-component protein complex that include several proteases. Work from Elaine Neale’s group has shown that part of the lethal effect of botulinum toxin A, considered a potential agent of terrorism, may be attributable to the severe retardation of the rate of replenishment of synaptic vesicles in the readily releasable pool at the nerve terminal, leading to a failure in neurotransmission.