The Developmental Biology of Neural Tube Formation

Morphogenesis, the process of cellular organization, determines the form and function of the organs. A relatively few cellular behaviors are responsible for all of morphogenesis: these include changes in cell shape, motility, adhesion, proliferation and differentiation. These changes are initiated, controlled and integrated by effectors in a cell’s microenvironment, especially extracellular matrix components, growth factors, cell surface proteins, proteases and anti-proteases. Cell surface receptors mediate the action of these effectors and mutations in these molecules and their receptors can cause abnormalities in morphogenesis. The CNS is the first organ system to undergo morphogenesis during embryogenesis. A series of landmark studies by the late Dr. Merton Bernfield in this IDDRC focused on the role of the syndecans, a family of heparan sulfate proteoglycans, and on the curly-tail mouse, a mouse model of human neural tube defects in morphogenesis (for key initial reports see Develop. Biol., 1991; Development, 1991; Genomics, 1991; J. Biol. Chem., 1993; PNAS, 1994; J. Biol. Chem., 1994; Nature Genomics, 1994).

The major findings of Dr. Bernfield and his colleagues have included: delineation of syndecans as a family of heparan sulfate proteoglycans crucial for "binding together" of components of the cellular microenvironment with the cytoskeleton; definition of syndecan as a "coreceptor" for bFGF and fibronectin and crucial for the action of such external effectors in CNS morphogenesis; determination of the importance of syndecans in reparative as well as developmental events; development of  mouse models, e.g., the curly-tail mutant, that mimics human neural tube defects; and definition of the functional and biochemical disturbance in the curly-tail mutant and mapping of the defective gene.