Fibroblast growth factors (FGFs) secreted from the midbrain-rhombomere 1 (r1) boundary instruct cell behavior in the surrounding neuroectoderm. For example, a combination of FGF and sonic hedgehog (SHH) can induce the development of the midbrain dopaminergic neurons, but the mechanisms behind the action and integration of these signals are unclear. We studied how FGF receptors (FGFRs) regulate ...

Sry high mobility group (HMG) box (Sox) transcription factors are involved in the development of central nervous system (CNS) in all metazoans. Little is known on the molecular mechanisms that regulate their transcriptional activity. Covalent posttranslational modification by small ubiquitin-like modifier (SUMO) regulates several nuclear events, including the transcriptional activity of transcr...

Gonadal dysgenesis with XY male-to-female sex reversal has been attributed to mutations and gene dosage differences in at least seven genes. We present a family of three sisters with a pure gonadal dysgenesis (Swyer syndrome) with an 46, XY karyotype. The sisters have a common X-chromosomal haplotype in Xp21.3-p11.3, the region of the X-chromosomal Swyer syndrome which includes NR0B1. We exclud...

Embryo development proceeds from a cascade of gene activation and repression events controlled by epigenetic modifications of DNA and histones. Little is known about epigenetic states in the developing zebrafish, despite its importance as a model organism. We report here DNA methylation and histone modification profiles of promoters of developmentally-regulated genes (pou5f1, sox2, sox3, klf4, ...

Mutations in the ATRX gene on the human X chromosome cause X-linked alpha-thalassemia and mental retardation. XY patients with deletions or mutations in this gene display varying degrees of sex reversal, implicating ATRX in the development of the human testis. To explore further the role of ATRX in mammalian sex differentiation, the homologous gene was cloned and characterized in a marsupial. S...

Sex chromosomes and the sex-determining (SD) gene are variable in vertebrates. In particular, medaka fishes in the genus Oryzias show an extremely large diversity in sex chromosomes and the SD gene, providing a good model to study the evolutionary process by which they turnover. Here, we investigated the sex determination system and sex chromosomes in six celebensis group species. Our sex-linka...

Lens development provides a good model system for studying cellular and molecular mechanisms underlying embryonic induction and morphogenesis. Members of the large Maf family of transcription factors, L-Maf and c-Maf, have been shown to play key roles in chick and mouse lens development. Here we report identification of two Xenopus maf genes, XmafB and XL-maf, which exhibit unique temporal and ...

Steroidogenic factor 1 (SF-1) is an essential factor in endocrine proliferation and gene expression. Despite the fact that SF-1 expression is restricted to specialized cells within the endocrine system, the only identified regulatory factors of SF-1 are the ubiquitously expressed E-box proteins (upstream stimulatory factors 1 and 2). Sequence examination of the SF-1 proximal promoter revealed a...

The cornea is a central component of the camera eye of vertebrates and even slight corneal disturbances severely affect vision. The transcription factor PAX6 is required for normal eye development, namely the proper separation of the lens from the developing cornea and the formation of the iris and anterior chamber. Human PAX6 mutations are associated with severe ocular disorders such as anirid...

development. Proc. Natl. Acad. Sci. U. S. A. 90, 3368–3372 6 Vidal, V.P. et al. (2001) Sox9 induces testis development in XX transgenic mice. Nat. Genet. 28, 216–217 7 Zhang, J. et al. (1999) In vitro binding and expression studies demonstrate a role for the mouse Sry Q-rich domain in sex determination. Int. J. Dev. Biol. 43, 219–227 8 Capel, B. et al. (1993) Circular transcripts of the testis-...