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Members of the yeast polymerase-associated factor 1 (Paf1) complex, which is composed of at least five components (Paf1, Rtf1, Cdc73, Leo1 and Ctr9), are conserved from yeast to humans. Although these proteins have been implicated in RNA polymerase II-mediated transcription, their roles in vertebrate development have not been explained. Here, we show that a zebrafish mutant with a somite segmentation defect is deficient in rtf1. In addition, embryos deficient in rtf1 or ctr9 show abnormal development of the heart, ears and neural crest cells. rtf1 is required for correct RNA levels of the Notch-regulated genes her1, her7 and deltaC, and also for Notch-induced her1 expression in the presomitic mesoderm. Furthermore, the phenotype observed in rtf1-deficient mutants is enhanced by an additional deficiency in mind bomb, which encodes an effector of Notch signalling. Therefore, zebrafish homologues of the yeast Paf1 complex seem to preferentially affect a subset of genes, including Notch-regulated genes, during embryogenesis.

Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells. SOCS proteins also regulate innate immune cells and are involved in tumorigenesis. This review summarizes recent progress on CIS, SOCS1, and SOCS3 in T cells and tumor immunity.

The larval ascidian brain (sensory vesicle) is located on the dorsal side of the trunk region and forms part of the anterior central nervous system. Sensory organs such as the otolith, ocellus, and hydrostatic-pressure organ reside in the brain. The brain coordinates the core roles of the larval nervous system. The brain is derived from anterior animal a-line blastomeres. The default fate of these blastomeres is epidermis, and the inductive signals from anterior vegetal blastomeres convert the fate into brain. It remains unclear, however, when these inductive interactions take place. To determine when, we examined whether partial embryos derived from brain-lineage blastomeres isolated at various stages express neural and epidermal marker genes. Partial embryos derived from brain-lineage blastomeres isolated after the 32-cell stage expressed all the neural marker genes examined. The expression of the epidermal marker gene was first reduced in partial embryos when blastomeres were isolated at the 64-cell stage. Moreover, the process for brain specification seemed to continue after the 110-cell stage. We also investigated the function of HrEts, an ascidian homolog of Ets transcription factors, to elucidate the molecular mechanism of brain induction. HrEts functions were inhibited by the use of antisense morpholino oligonucleotides. Loss of Ets functions resulted in loss of the expression of some of the neural marker genes and the ectopic expression of the epidermal marker gene in brain precursor cells. These results suggest that HrEts is an essential transcription factor that mediates ascidian brain induction.

Notch signaling plays crucial roles during embryogenesis in various metazoans. HrNotch, a Notch homologue in the ascidian Halocynthia roretzi, has been previously cloned, and its expression pattern suggests that HrNotch signaling is involved in nervous system formation. To determine the function of HrNotch signaling, in the present study we examined the effects of the constitutively activated forms of HrNotch. Overexpression resulted in larvae with defects in neural tube closure and brain vesicle formation. In embryos expressing the activated HrNotch, the expression of a neural marker gene, HrETR-1, was enhanced and expanded in the central nervous system, although ectopic expression decreased during the tailbud stage. The activated HrNotch also suppressed the formation of the adhesive organ (palps) and the peripheral nervous system, which consists of ciliary mechanosensory neurons, whereas it promoted epidermal differentiation. The suppression and promotion of the formation of these respective cell types were confirmed by examination of the expression of relevant tissue-specific markers. We also cloned HrDelta, an ascidian homologue of DSL family genes, which encode ligands for which Notch acts as a receptor. The expression of HrDelta was observed in the precursors of palps and peripheral neurons in addition to the CNS. These results suggest that Notch signaling is important for ascidian nervous system formation and that it affects the fate choice between palps and epidermis and between peripheral neurons and epidermis within the neurogenic regions of the surface ectoderm by suppressing the formations of palps and peripheral neurons and promoting epidermal differentiation.