RETRACTED: Dynamic expression and regulation by Fgf8 and Pou2 of the zebrafish LIM-only gene, lmo4

{ "0" : "Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street/LRB822, Worcester, MA 01605, USA" , "2" : "Mary Ellen Lane, Alexander P Runko, Nicole M Roy, Charles G Sagerström"}
Gene Expression Patterns (Impact Factor: 1.38). 12/2002; 119(3). DOI: 10.1016/S0925-4773(03)00114-X


We report the expression of zebrafish lmo4 during the first 48 h of development. Like its murine ortholog, lmo4 is expressed in somitic mesoderm, branchial arches, otic vesicles, and limb (pectoral fin) buds. In addition, however, we report zebrafish lmo4 expression in the developing eye, cardiovascular tissue, and the neural plate and telencephalon. We demonstrate that expression in the rostral hindbrain requires acerebellar (ace/fgf8) and spielohnegrenzen (spg/pou2) activity.

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Available from: Mary Ellen Lane, Oct 21, 2014
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    • "Ppargc1b is a coactivator of peroxisome proliferator activated receptor gamma (PPARγ), involved in lipid metabolism and regulates oxidative metabolism [21]. Lmo4a (LMO4 in human) is expressed in the telencephalon in zebrafish [22]. In humans, LMO4 is a suspected oncogene since it is found to be inhibiting the breast cancer type 1 susceptibility protein (BRCA1) activity [23]. "
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    ABSTRACT: Brain aging is a multi-factorial process due to both genetic and environmental factors. The zebrafish has recently become a popular model organism for examining aging and age-related diseases because as in humans they age gradually and exhibit cognitive decline. Few studies have examined the biological changes in the aging brain that may contribute to these declines and none have examined them within individuals with respect to gender. Our aim was to identify the main genetic pathways associated with zebrafish brain aging across gender. We chose males and females from specific age groups (young, 7.5-8.5 months and old, 31-36 months) based on the progression of cognitive decline in zebrafish. RNA was isolated from individual brains and subjected to microarray and qPCR analysis. Statistical analyses were performed using a two-way ANOVA and the relevant post-hoc tests. Our results demonstrated that in the brains of young and old male and female zebrafish there were over 500 differentially expressed genes associated with multiple pathways but most notably were those related to neurogenesis and cell differentiation, as well as brain and nervous system development. The gene expression of multiple pathways is altered with age and differentially expressed in males and females. Future studies will be aimed at determining the causal relationships of age-related changes in gene expression in individual male and female brains, as well as possible interventions that counteract these alterations.
    Full-text · Article · Feb 2014 · BMC Neuroscience
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    • "Within the highly homologous LMO family, LMO4 is the most divergent and is the least well studied factor. It has been reported to be expressed in the thymus, brain, skin, pituitary gland, nervous system as well as the neural crest (Bach, 2000; Lane et al., 2002; McCollum et al., 2007; Setogawa et al., 2006; Sum et al., 2005). Interestingly, LMO4 is also highly expressed in breast cancer cells and at locations of active mesenchymal–epithelial interactions (Lu et al., 2006). "
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    ABSTRACT: The neural crest (NC) is a population of multipotent stem cell-like progenitors that arise at the neural plate border in vertebrates and migrate extensively before giving rise to diverse derivatives. A number of components of the neural crest gene regulatory network (NC-GRN) are used reiteratively to control multiple steps in the development of these cells. It is therefore important to understand the mechanisms that control the distinct function of reiteratively used factors in different cellular contexts, and an important strategy for doing so is to identify and characterize the regulatory factors they interact with. Here we report that the LIM adaptor protein, LMO4, is a Slug/Snail interacting protein that is essential for NC development. LMO4 is expressed in NC forming regions of the embryo, as well as in the central nervous system and the cranial placodes. LMO4 is necessary for normal NC development as morpholino-mediated knockdown of this factor leads to loss of NC precursor formation at the neural plate border. Misexpression of LMO4 leads to ectopic expression of some neural crest markers, but a reduction in the expression of others. LMO4 binds directly to Slug and Snail, but not to other components of the NC-GRN and can modulate Slug-mediated neural crest induction, suggesting a mechanistic link between these factors. Together these findings implicate LMO4 as a critical component of the NC-GRN and shed new light on the control of Snail family repressors.
    Full-text · Article · Nov 2011 · Developmental Biology
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    • "Lane, in preparation). In contrast to mouse Lmo4, zebrafish lmo4b is not highly expressed in the proliferative ventricular zone throughout the neural tube (Lane et al., 2002). Although mammalian Lmo4 is also expressed in anterior neural tissue (Lee et al., 2005), early expression of mammalian Lmo4 at the anterior neural plate boundary has not been described. "
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    ABSTRACT: The Six3 and Rx3 homeodomain proteins are essential for the specification and proliferation of forebrain and retinal precursor cells of the vertebrate brain, and the regulatory networks that control their expression are beginning to be elucidated. We identify the zebrafish lmo4b gene as a negative regulator of forebrain growth that acts via restriction of six3 and rx3 expression during early segmentation stages. Loss of lmo4b by morpholino knockdown results in enlargement of the presumptive telencephalon and optic vesicles and an expansion of the post-gastrula expression domains of six3 and rx3. Overexpression of lmo4b by mRNA injection causes complementary phenotypes, including a reduction in the amount of anterior neural tissue, especially in the telencephalic, optic and hypothalamic primordia, and a dosage-sensitive reduction in six3 and rx3 expression. We suggest that lmo4b activity is required at the neural boundary to restrict six3b expression, and later within the neural plate to for attenuation of rx3 expression independently of its effect on six3 transcription. We propose that lmo4b has an essential role in forebrain development as a modulator of six3 and rx3 expression, and thus indirectly influences neural cell fate commitment, cell proliferation and tissue growth in the anterior CNS.
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