The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal cell development and encodes a zinc finger protein.

Basson, Michael; Horvitz, H. Robert

doi:10.1101/gad.10.15.1953

Cited by 75 publications

(76 citation statements)

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“…We focused on transcription factors that have been previously shown to display either all or a subset of the ham-3 phenotypes (Table 1): unc-86, a Brn3-type POU homeobox gene (Finney et al 1988); sem-4, a Spalt/SALL-type Zn finger transcription factor (Basson and Horvitz 1996); and ham-2, a member of a divergent C2H2 Zn finger family that expanded specifically in C.elegans (Baum et al 1999; Zhang et al 2011). unc-86 and sem-4 are known to be required for expression of serotonin in HSN, but not for HSN migration (Desai et al 1988;Basson and Horvitz 1996;Sze et al 2002), and ham-2 is known to be required for HSN migration, but not serotonin pathway expression (Baum et al 1999). We find that the expression of sem-4 and ham-2 expression is strongly defective in the HSNs of ham-3(n1654) mutants, while unc-86 expression is barely affected (Figure 4, A-C).…”

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“…These mutant analyses revealed genes that are involved in controlling multiple aspects of HSN development and function, and genes that control only a select number of HSN features (Desai et al 1988) (Table 1). For example, the egl-5 HOX cluster gene controls all known aspects of HSN development and function, while the unc-86 POU homeobox and sem-4 Zn finger transcription factor control serotonin expression and axon pathfinding, but not neuronal migration (Basson and Horvitz 1996;Sze et al 2002). Conversely, the ham-2 Zn finger transcription factor controls HSN migration, but not serotonin expression (Baum et al 1999).…”

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The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

et al. 2013

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Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene, ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in ham-3 null mutants, demonstrating that ham-3 is a specific regulator of select features of the HSNs. We show that ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of ham-3 on serotonergic fate can be explained by ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor sem-4, a previously identified regulator of serotonin expression in HSNs and of the ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development. N EURONS that express the neurotransmitter serotonin fulfill a number of critical functions in all nervous systems examined to date. In vertebrates, serotonergic neurons modulate anxiety, cognitive processes, mood, body temperature, sleep, sexual behavior, appetite, and metabolism, and their dysfunction has been connected to a variety of human disorders (Muller and Jacobs 2010). In the hermaphroditic Caenorhabditis elegans nervous system, serotonin also controls a number of distinct behaviors (Schafer 2005;Chase and Koelle 2007). Serotonin is utilized as a neurotransmitter under normal conditions by seven neuron types, the sensory neuron ADF; the interneurons AIM and RIH; the motor neurons hermaphroditespecific neurons (HSNs), the ventral cord motor neurons VC4 and VC5; and the neurosecretory NSM cells (Schafer 2005;Chase and Koelle 2007). Under stress conditions, serotonin is used by an additional neuron type, ASG (Pocock and Hobert 2010). One of the serotonergic neurons, the hermaphrodite-specific motor neuron, HSN, utilizes serotonin to signal to vulval muscles to control egg-laying behavior (Schafer 2005). Unlike most other neurons in the C. elegans nervous system, the two bilaterally symmetric HSNs undergo long-range migration. After terminating migration, they extend th...

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The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

et al. 2013

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“…It plays an important role in terminal differentiation of photoreceptors, tracheal development, 5 and wing vein placement. 6 Sal-related genes have been isolated from Caenorhabditis elegans, 7 fish, 8,9 Xenopus, 10,11 mice, 12,13 and humans. 14 Each of these homologs is expressed during embryonic development and in specific adult tissues.…”

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Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Cui

Kong

Ma³

et al. 2006

Modern Pathology

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CanadaSALL4, a newly identified zinc-finger transcriptional factor important for embryonic development, is mapped to chromosome 20q13. Previously, we reported that SALL4 was constitutively expressed in acute myeloid leukemia and SALL4 transgenic mice developed acute myeloid leukemia. In this study, we aimed to survey SALL4 protein expression in benign and neoplastic hematopoietic tissues in addition to acute myeloid leukemia using immunostaining with a polyclonal anti-SALL4 antibody. Primary hematological tumors (178) and 15 benign hematopoietic tissues were examined. Reverse transcription-polymerase chain reaction was also performed to detect SALL4 mRNA expression on eight precursor B-cell lymphoblastic leukemia/lymphomas, 10 benign hematopoietic tissues, and seven hematopoietic cancer cell lines. Of the benign tissues, SALL4 expression was detectable only in CD34 þ hematopoietic stem/progenitor cells (2/2 at protein level, 3/3 at RNA level). In neoplastic tissues, only precursor B-cell lymphoblastic leukemia/lymphomas had detectable SALL4 (12/16 at protein level, 7/8 at RNA level), similar to that observed in acute myeloid leukemia. Of the seven cell lines examined, only those derived from acute myeloid leukemia and precursor B-cell lymphoblastic leukemia/ lymphomas were positive. To conclude, SALL4 expression is normally restricted to CD34 þ hematopoietic stem/ progenitor cells. The persistence of SALL4 expression in leukemic blasts in precursor B-cell lymphoblastic leukemia/lymphomas resembles to what we observed in acute myeloid leukemia, and correlates with the maturation arrest of these cells. We have shown in our previous study that the constitutive expression of SALL4 in mice can lead to acute myeloid leukemia development. The similar expression pattern of SALL4 in acute myeloid leukemia and B-cell lymphoblastic leukemia/lymphomas suggests that these two disease entities may share similar biological features and/or mechanisms of leukemogenesis. More definite studies to investigate the role of SALL4 in the pathogenesis of B-cell lymphoblastic leukemia/lymphomas are needed in the future to address this question.

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“…Consistent with TBS phenotypes, human SALL1 expression has been detected in the brain, heart, ureteric bud, and developing tubules of the kidney, testes, and ovary (2, 17). In mice, sal genes are expressed in brain, testes, ovaries, kidneys, limb buds, heart, inner ear, and the lens of the eye (18,19).spalt genes have been identified in a variety of vertebrates and invertebrates (2,3,18,(20)(21)(22)(23)(24)(25)(26)(27)(28). In Drosophila, there are two adjacent spalt genes, spalt (sal) and spalt-related (salr).…”

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“…spalt genes have been identified in a variety of vertebrates and invertebrates (2,3,18,(20)(21)(22)(23)(24)(25)(26)(27)(28). In Drosophila, there are two adjacent spalt genes, spalt (sal) and spalt-related (salr).…”

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Drosophila spalt/spalt-related mutants exhibit Townes-Brocks' syndrome phenotypes

Dong

Todi

Eberl

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in SALL1, the human homolog of the Drosophila spalt gene, result in Townes-Brocks' syndrome, which is characterized by hand͞foot, anogenital, renal, and ear anomalies, including sensorineural deafness. spalt genes encode zinc finger transcription factors that are found in animals as diverse as worms, insects, and vertebrates. Here, we examine the effect of losing both of the spalt genes, spalt and spalt-related, in the fruit fly Drosophila melanogaster, and report defects similar to those in humans with Townes-Brocks' syndrome. Loss of both spalt and spalt-related function in flies yields morphological defects in the testes, genitalia, and the antenna. Furthermore, spalt͞spalt-related mutant antennae show severe reductions in Johnston's organ, the major auditory organ in Drosophila. Electrophysiological analyses confirm that spalt͞spalt-related mutant flies are deaf. These commonalities suggest that there is functional conservation for spalt genes between vertebrates and insects.Distal-less ͉ homothorax ͉ atonal ͉ chordotonal organ ͉ split hand͞split foot malformation T ownes-Brocks' syndrome (TBS) is an autosomal dominant disorder that maps to the SALL1 locus at 16q12.1 (1). SALL1 is one of three known vertebrate homologs of Drosophila spalt (sal) (2, 3). The mutations in SALL1 that result in TBS typically lead to a premature stop codon after the first zinc finger (1, 4-7). Although the clinical manifestations of TBS are variable, Ϸ85% of patients with TBS exhibit hand͞foot, anogenital, renal, and ear anomalies, including sensorineural deafness (8-13). TBS is estimated to occur in 1:250,000 liveborn (14), but may be misdiagnosed because its defects overlap with those of other genetic diseases (7,11,15,16). Consistent with TBS phenotypes, human SALL1 expression has been detected in the brain, heart, ureteric bud, and developing tubules of the kidney, testes, and ovary (2, 17). In mice, sal genes are expressed in brain, testes, ovaries, kidneys, limb buds, heart, inner ear, and the lens of the eye (18,19).spalt genes have been identified in a variety of vertebrates and invertebrates (2,3,18,(20)(21)(22)(23)(24)(25)(26)(27)(28). In Drosophila, there are two adjacent spalt genes, spalt (sal) and spalt-related (salr). These genes use shared regulatory regions and are expressed in similar patterns throughout development. Early studies of sal single mutants indicated that sal is required for the development of the embryonic terminalia, tracheal system, and wings (20,(29)(30)(31)(32). Mutations in sal result in partial transformations of the posterior head and anterior tail toward trunk identity (20). sal functions during tracheal development both to restrict the positions of the initial placodes and in directed migration of dorsal trunk cells (30). At larval stages, Dpp-activated sal expression in the wing pouch is activated in response to graded levels of Dpp to properly position wing pattern elements (29,31,33).More recent studies of Drosophila lacking the function of both sal and salr indicate that there ...

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The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal cell development and encodes a zinc finger protein.

Cited by 75 publications

References 57 publications

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia

Drosophila spalt/spalt-related mutants exhibit Townes-Brocks' syndrome phenotypes

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