PATTERNS OF NEURONAL DIFFERENTIATION IN NEURAL-TUBE MUTANT MICE - CURLY TAIL AND PAX3 SPLOTCH-DELAYED

A battery of antibodies was used to assess development of the spinal c ord and its neurons in mouse embryos with neural tube defects (NTDs). The two mutant strains examined, curly tail (ct) and splotch-delayed ( Pax3(Sp-d)), develop an open neural tube for unrelated reasons, and th us provided for a complementary analysis. Five percent of embryos homo zygous for the ct gene and 89% of embryos homozygous for the Pax3(Sp-d ) gene develop spina bifida in the lumbosacral region of the neuraxis. Expression of several neuronal antigens, including Islet-1/2, polysia lylated neural cell adhesion molecule (NCAM), neurofilaments, and a ne uronal-specific nuclear protein (NeuN) recognized by monoclonal antibo dy A60, were used as indicators of the level of differentiation of neu ronal tissue. Immunohistochemical labeling suggests that early (embryo nic days 12-15) neuronal differentiation in the dorsal and ventral reg ion of the dysraphic neural tube occurs remarkably normally in both of the mutants. Similarly, labeling with antibodies to NCAM and neuroafi laments indicate that axonal development during early neurogenesis is unperturbed. Later stages of neuronal maturation, however, do not occu r in the usual manner. Instead, the neuronal tissue begins a prodigiou s degeneration at embryonic day 17 (E17), so that by E18 only a rudime ntary tissue remains. These results suggest that the aberrant morpholo gy of the neural tube does not affect neuronal differentiation. Howeve r, the anomalous morphological and chemical environment may contribute to the neuronal degeneration observed at later stages. (C) 1996 Wiley -Liss, Inc.