Sox proteins of group C are strongly expressed in the developing nervous system and have been associated with maturation of neurons and glia. Here, we overexpressed the group C protein Sox4 in transgenic mice under the control of the human GFAP promoter. Transgene expression was detected in radial glia and astrocytes throughout the CNS. The transgenic mice were ataxic and exhibited hydrocephaly as well as cerebellar malformations. In the cerebellum, fissures were not formed and neuronal layering was dramatically disturbed. Nevertheless, all neuronal cell types of the cerebellum were present as well as cells with characteristics of early radial glia, astrocytes, and oligodendrocytes. However, radial glia failed to migrate into the position normally taken by Bergmann glia and did not extend radial fibers toward the pial surface. The cerebellar malformations can therefore be explained by the absence of functional Bergmann glia. We conclude that Sox4 expression counteracts differentiation of radial glia and has to be downregulated before full maturation can occur.

The sequence of events and a possible reason for germ cell death during oogenesis in the prenatal ovary were studied in rat and mouse embryos. ED 14-22 rat and ED 14-16 mouse embryos were studied using semithin sections for light microscopy and serial ultrathin sections for electron microscopy. In addition, the rat material was 3H-thymidine labelled for historadioautography and cytospin preparations of freshly obtained gonads were immunohistochemically analysed. During the transition from the proliferating oogonial stage to the meiotic prophase about 16% of the postmitotic oocytes do not pass the initial meiotic checkpoint on ED 18/19 in the rat (ED 15/16 in the mouse). These germ cells first show structural signs of mitosis; the diploid number of 'super-condensed' chromosomes are globally formed and are concentrated in the center of the cell. Although the germ cells show all morphological signs of living cells they never have mitotic spindles; the micro-tubulus-organisation-centres (MTOCs) are found peripherally and become concentrated, forming a single centrosomal body (acentriolar MTOC) as detected by immunohistochemistry for the centrosomal protein MPM2 and gamma-tubulin. EM studies show 25 nm tubule-like profiles within the MTOC bodies. The centrioles frequently lie separate from the MTOC material or are not present at all; the germ cells are apparently arrested in a prophase- or metaphase-like stage when they have reached the postmitotic G2/preleptotenal transition and are unable to enter meiosis. Forty-eight to 72 h after the first mitotically arrested germ cells are found, degeneration is seen in these germ cells. This second event, the germ cell death proper, shows neither criteria of apoptosis (cell shrinkage, marginal condensation of chromatin, DNA fragmentation) nor signs of necrosis (cell swelling, pycnosis, inflammation). Both arrested pro- and metaphase-like stages are found with signs of cell death and phagocytosis. The morphological signs of phagocytosis are found in neighbouring pregranulosa cells. The final heterocytotic bodies contain the remnants of the centrosomal (MTOC) material and DAPI-positive DNA material. The pregranulosa cells are mitotically silent during the phase when mitotic arrest and germ cell degeneration is found. The results suggest the presence of a hypothetical 'anti-spindle' factor, which under normal conditions is necessary for induction of meiotic prophase. The structural events of 'arrested mitosis' is reminiscent of those induced by the antimitotic, tubule-degrading drug colcemid. This type of arrest may inhibit meiosis of more than 33% prenatal germ cells and induce their cell death.

Mesonephric agenesis was achieved by microsurgical excision of the left Wolffian duct and the underlying intermediate mesoderm of different regions between somites 16 and 23 in chickens after 50–52 h of incubation (stage 14 HH). Quail-chick chimaeras were produced by transplantation of corresponding quail tissue in the region of somites 18–21. A morphometrical analysis of the mesonephric and gonadal area in cross sections shows that the intermediate mesoderm from somites 16 to 23 develops into the mesonephros. A partial agenesis of the mesonephros brought about by removal of the intermediate mesoderm at the level of somites 18 to 21 at stage 14 leads to a mean reduction of the gonadal volume of 37·8% compared to the volume of the untreated side at stage 30. Transplantation of quail intermediate mesoderm in this region of the excision results in development of a hybrid mesonephros. Consequently, the gonads are invaded and colonized by quail cells mobilized from mesonephric corpuscles examined at stage 30, 35 and 36. These results are discussed in terms of the origin of the gonadal stroma during this developmental period; they show that in the region from the third to the sixth segment the ventromedial part of the differentiating mesonephros participates in the contribution of stromal cells to the gonad.