Myogenin is a muscle-specific transcription factor that can induce myogenesis in a variety of cell types in tissue culture. To test myogenin's role in vivo, mice homozygous for a targeted mutation in the myogenin gene were generated. These mice survive fetal development but die immediately after birth and show a severe reduction of all skeletal muscle. Myogenin-mutant mice differ from mice carrying mutations in genes for the related myogenic factors Myf5 and MyoD, which have no muscle defects. Myogenin is therefore essential for the development of functional skeletal muscle.

The mammalian circadian clock lying in the suprachiasmatic nucleus (SCN) controls daily rhythms and synchronizes the organism to its environment. In all organisms studied, circadian timekeeping is cell-autonomous, and rhythmicity is thought to be generated by a feedback loop involving clock proteins that inhibit transcription of their own genes. In the present study, we examined how these cellular properties are organized within the SCN tissue to produce rhythmicity and photic entrainment. The results show that the SCN has two compartments regulating Period genes Per1, Per2, and Per3 mRNA expression differentially. One compartment shows endogenous rhythmicity in Per1, Per2, and Per3 mRNA expression. The other compartment does not have rhythmic mRNA expression but has gated light-induced Per1 and Per2 and high levels of endogenous nonrhythmic Per3 mRNA expression. These results reveal the occurrence of differential regulation of clock genes in two distinct SCN regions and suggest a potential mechanism for producing functional differences in distinct SCN subregions.

Abstract. Mice with a targeted mutation in the myogenic basic helix-loop-helix regulatory protein myogenin have severe muscle defects resulting in perinatal death. In this report, the effect of myogenin's absence on embryonic and fetal development is investigated. The initial events of somite differentiation occurred normally in the myogenin-mutant embryos. During primary myogenesis, muscle masses in mutant embryos developed simultaneously with control siblings, although muscle differentiation within the mutant muscle masses was delayed. More dramatic effects were observed when secondary myofibers form. During this time, very little muscle formation took place in the mutants, suggesting that the absence of myogenin affected secondary myogenesis more severely than primary myogenesis. Monitoring mutant neonates with fiber type-specific myosin isoforms indicated that different fiber types were present in the residual muscle. No evidence was found to indicate that myogenin was required for the formation of muscle in one region of the embryo and not another. The expression patterns of a MyoD-lacZ transgene in myogenin-mutant embryos demonstrated that myogenin was not essential for the activation of the MyoD gene. Together, these results indicate that late stages of embryogenesis are more dependent on myogenin than early stages, and that myogenin is not required for the initial aspects of myogenesis, including myotome formation and the appearance of myoblasts. SKELETAL muscle in vertebrates originates from somitic mesoderm as pluripotent mesodermal cells become committed to a myogenic fate. Committed myoblasts populate areas throughout the developing embryo, ultimately differentiating into bundles of multinucleate myofibers. Four key players in myogenic events are the basic helix-loop-helix (bHLH) ~ regulatory proteins: MyoD, Myf5, myogenin, and MRF4 (for recent reviews see Emerson, 1993;Weintraub, 1993;Olson and Klein, 1994). These muscle-specific transcription factors are individually able to initiate the entire muscle differentiation program when introduced into tissue culture cells of nonmuscle origin. Using gene-knockout technology, several laboratories have created mice lacking functional myogenic bHLH factors and are now providing useful models for studying skeletal muscle development (Braun et al

Components of the Wnt signaling pathway are involved in patterning the sea urchin primary or animal-vegetal (AV) axis, but the molecular cues that pattern the secondary embryonic axis, the aboral/oral (AO) axis, are not known. In an analysis of signaling molecules that influence patterning along the sea urchin embryonic axes, we found that members of the activin subfamily of transforming growth factor-␤ (

The mechanism of animal-vegetal (AV) axis formation in the sea urchin embryo is incompletely understood. Specification of the axis is thought to involve a combination of cell-cell signals and as yet unidentified maternal determinants. In Xenopus the Wnt pathway plays a crucial role in defining the embryonic axes. Recent experiments in sea urchins have shown that at least two components of the Wnt signaling pathway, GSK3beta and beta-catenin, are involved in embryonic AV axis patterning. These results support the notion that the developmental network that regulates axial patterning in deuterostomes is evolutionarily conserved. To further test this hypothesis, we have examined the role of beta-catenin nuclear binding partners, members of the TCF family of transcriptional regulators, in sea urchin AV axis patterning. To test the role of TCFs in mediating beta-catenin signals in sea urchin AV axis development we examined the consequences of microinjecting RNAs encoding altered forms of TCF on sea urchin development. We show that expression of a dominant negative TCF results in a classic "animalized" embryo. In contrast, microinjected RNA encoding an activated TCF produces a highly "vegetalized" embryo. We show that the transactivational activity of endogenous sea urchin TCF is potentiated by LiCl treatment, which vegetalizes embryos by inhibiting GSK3, consistent with an in vivo interaction between endogenous beta-catenin and TCF. We also provide evidence indicating that all of beta-catenin's activity in patterning the sea urchin AV axis is mediated by TCF. Using a glucocorticoid-responsive TCF, we show that TCF transcriptional activity affects specification along the AV axis between fertilization and the 60-cell stage.