High impact information on zfh1

• The Spotted-dick Zinc-finger protein is present in the nuclei of cells committed to proliferation but necessary in cells undertaking S phase [1].
• One such zinc finger/homeodomain protein is Drosophila Zfh-1, a member of the zfh family of Drosophila genes, which is expressed in muscle precursors and is critical for the proper development of muscle [2].
• ZEB, a vertebrate homolog of Zfh-1, binds a subset of E boxes and blocks myogenesis through transcriptional repression of muscle genes [3].
• Binding sites for zfh-1 overlap with those for snail, and like snail, it recruits the corepressor CtBP-1 [4].
• The protein ZEB-1 appears to be a vertebrate homologue of zfh-1 and is expressed in several tissues including muscle, CNS, and T lymphocytes, and during skeletal differentiation [4].

Biological context of zfh1

• Specification of the ISN subclass is dependent upon both even-skipped (eve) and the zfh1 zinc-finger homeobox gene [5].
• Here, we demonstrate that zfh-1 is a transcription factor that binds E box sequences and acts as an active transcriptional repressor [6].
• ZEB inhibits muscle differentiation in mammalian systems, and its Drosophila orthologue, zfh-1, inhibits somatic and cardiac muscle differentiation during Drosophila embryogenesis [7].
• When zfh-1 expression was maintained in the embryo beyond its normal temporal pattern of downregulation, the differentiation of somatic but not visceral muscle was blocked [6].
• The Drosophila homeobox genes zfh-1 and even-skipped are required for cardiac-specific differentiation of a numb-dependent lineage decision [8].

Anatomical context of zfh1

• In zfh1 mutants, ventral projecting motor axons often stall at the edge of the CNS, failing to enter the muscle field, despite having normal motor neuron identity [9].
• Zfh1 is detected in all embryonic somatic motor neurons, glia associated with the CNS surface and motor axons, and one identified interneuron [9].
• The zfh-1 gene is expressed in the mesoderm of early embryos and in a number of mesodermally-derived structures of late embryos, including the dorsal vessel, support cells of the gonads, and segment-specific arrays of adult muscle precursors [10].
• Its homologue in Drosophila (zfh-1) is also essential for differentiation of somatic and cardiac muscle [11].
• zfh-1 is a zinc finger/homeodomain transcriptional repressor in Drosophila that regulates differentiation of muscle and gonadal cells and is also expressed in the central nervous system (CNS) [4].

Associations of zfh1 with chemical compounds

• NAC1 is a member of the Bric-a-brac Tramtrac Broad complex/Pox virus and Zinc finger family of transcription factors and has been shown by overexpression studies to prevent the development of behavioral sensitization resulting from repeated cocaine treatment [12].

Regulatory relationships of zfh1

• Embryonic enhancers in the dpp disk region regulate a second round of Dpp signaling from the dorsal ectoderm to the mesoderm that represses Zfh-1 expression in a subset of pericardial cells [13].
• Zfh-1 is also expressed in the gonadal mesoderm throughout the development of this tissue [14].

Other interactions of zfh1

• The Drosophila zfh-1 and zfh-2 genes encode novel proteins containing both zinc-finger and homeodomain motifs [15].
• I further show that likely EH1 motifs are found in combination with T-Box, Zinc Finger and Doublesex domains as well as discussing other plausible candidate associations [16].
• This round of dpp expression is also restricted to LE cells but Dpp signaling specifies the repression of the transcription factor Zfh-1 in a subset of pericardial cells in the underlying mesoderm [13].
• Here we describe the role of zfh-1 in germ cell migration to the gonadal mesoderm [14].
• Similar to tinman, the zinc finger- and homeobox-containing gene, zfh-1, is expressed in the early mesoderm and later in the forming heart, suggesting a possible role in heart development [8].

Analytical, diagnostic and therapeutic context of zfh1

• However, we have shown previously that another member of the family, the vertebrate ZEB protein, is a transcriptional repressor that binds E box sequences and inhibits myotube formation in cell culture assays. zfh-1 is downregulated in Drosophila embryos prior to myogenesis [6].

References