Molecular mediation of neural differentiation

The International Journal of Developmental Neuroscience just dedicated an issue in memory of Antonia Vernadakis, Ph.D., Professor of Pharmacology and Psychiatry, University of Colorado, an international leader in developmental neuroscience. Amongst her many contributions is that recognizing early on the importance of development in understanding CNS function, she and a handful of other neurobiologists initiated the formation of International Society for Developmental Neuroscience (ISDN) and the Society's Journal. Both forums have thrived and have developed into a considerable force in the ®eld of developmental neuroscience. The speci®c ®elds she foresaw and helped establish with her work were those of neuron± glia interactions, growth factor potential of neurotransmitters and hormones on the developing neuron and astrocyte, and regulation of astrocytic phenotypes. To celebrate these achievements the Journal decided to extend its tribute to Antonia with an issue consisting of contributions from colleagues who shared her vision and continue to shape the scienti®c culture in the developmental neuroscience ®eld. Therefore this issue is designed to provide novel views on molecules that govern neural induction and di€erentiation. The ®rst of these articles presents and discusses the elegant experiments by Marianne Bronner-Fraser and associates, which demonstrate the paracrine action of di€usable molecules in the induction of neural crest into speci®c cell fates. The next article focuses on the emerging role of the di€usable extracellular matrix proteoglycans as another mediator of both cell±cell and of cell±substratum signaling in early development patterning; Nancy Schwartz and colleagues present extensive biochemical studies on the role of proteoglycans as morphogenetic molecules in development and the early di€erentiation in proteoglycan species and synthesis between early postmitotic neurons and immature astrocytes. The contribution by Barbara Ranscht re ̄ects the important issue of speci®city in neuronal connections in development, that is, axonal path®nding and synapse formation are reviewed through the actions of the transmembrane cadherins with an emphasis on the new questions that have been generated by the recent expansion of the cadherin ®eld. The growth factor potential of neurotransmitters in normal development and teratogenecity is thoroughly reviewed and established using whole organism experiments for the serotonin receptors 5HTA±C by Jean Lauder and colleagues; the glutamate delta 2 receptor is the focus of the contribution by Annie Messer and co-author; and Anita Sidhu and coauthor focus on the dopamine receptors. In addition to neurotransmitters, peptide growth factors are most likely to serve neuron±glia interactions; an elegant example is presented for GDNF by Marty Bohn and colleagues, as well as for glial somatostatin-14, a novel glial-derived growth factor by Joan Schwartz and colleagues. Similarly, peptide hormones are key molecules in development and the role of prolactin and its receptor coupling to diverse signaling pathways is delineated in embryonic astrocytes by Mimika Mangoura and colleagues, where, in addition, the intriguing role of proliferation as part of bulk generation of di€erentiated astrocytes is established. Lastly, Sara Szuchet and colleagues establish the role of proteoglycans in postnatal di€erentiation of oligodendrocytes and provide evidence that this mechanism may be recapitulated during oligodendrocytic regeneration. To all of us who had the privilege to have known her as a teacher, as a colleague, as a friend, A.V. will be greatly missed.