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Your search keyword '"Hanel ML"' showing total 2 results
Start Over Author "Hanel ML" Topic gene expression regulation, developmental
2 results on '"Hanel ML"'

1. Muscular dystrophy candidate gene FRG1 is critical for muscle development.

Author

Hanel ML, Wuebbles RD, and Jones PL

Subjects
Animals, Humans, In Situ Hybridization, Microfilament Proteins, Muscle, Skeletal abnormalities, Muscle, Skeletal anatomy & histology, MyoD Protein genetics, MyoD Protein metabolism, Nuclear Proteins metabolism, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense metabolism, PAX3 Transcription Factor, Paired Box Transcription Factors genetics, Paired Box Transcription Factors metabolism, RNA-Binding Proteins, Xenopus Proteins genetics, Gene Expression Regulation, Developmental, Muscle Development genetics, Muscle, Skeletal embryology, Muscle, Skeletal growth & development, Muscular Dystrophy, Facioscapulohumeral genetics, Nuclear Proteins genetics, Xenopus Proteins metabolism, Xenopus laevis anatomy & histology, Xenopus laevis physiology
Abstract

The leading candidate gene responsible for facioscapulohumeral muscular dystrophy (FSHD) is FRG1 (FSHD region gene 1). However, the correlation of altered FRG1 expression levels with disease pathology has remained controversial and the precise function of FRG1 is unknown. Here, we carried out a detailed analysis of the normal expression patterns and effects of FRG1 misexpression during vertebrate embryonic development using Xenopus laevis. We show that frg1 is expressed in and essential for the development of the tadpole musculature. FRG1 morpholino injection disrupted myotome organization and led to inhibited myotome growth, while elevated FRG1 led to abnormal epaxial and hypaxial muscle formation. Thus, maintenance of normal FRG1 levels is critical for proper muscle development, supportive of FSHD disease models whereby misregulation of FRG1 plays a causal role underlying the pathology exhibited in FSHD patients. Developmental Dynamics 238:1502-1512, 2009. (c) 2008 Wiley-Liss, Inc.

Published
2009
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2. Eye and neural defects associated with loss of GDF6.

Author

Hanel ML and Hensey C

Subjects
Animals, Apoptosis genetics, Blotting, Western, Bone Morphogenetic Proteins deficiency, Bone Morphogenetic Proteins physiology, Embryo, Nonmammalian abnormalities, Embryo, Nonmammalian embryology, Embryo, Nonmammalian metabolism, Eye Proteins genetics, Eye Proteins metabolism, Growth Differentiation Factor 6, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Immunohistochemistry, In Situ Hybridization, In Situ Nick-End Labeling, Nervous System embryology, Nervous System metabolism, Nervous System pathology, Nervous System Diseases embryology, PAX6 Transcription Factor, Paired Box Transcription Factors genetics, Paired Box Transcription Factors metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Repressor Proteins genetics, Repressor Proteins metabolism, Retina abnormalities, Retina metabolism, Xenopus embryology, Xenopus Proteins deficiency, Xenopus Proteins genetics, Xenopus Proteins physiology, Bone Morphogenetic Proteins genetics, Eye Abnormalities genetics, Gene Expression Regulation, Developmental genetics, Nervous System Diseases genetics, Xenopus genetics
Abstract

Background: In Xenopus the bone morphogenetic protein growth and differentiation factor 6 (GDF6) is expressed at the edge of the neural plate, and within the anterior neural plate including the eye fields. Here we address the role of GDF6 in neural and eye development by morpholino knockdown experiments., Results: We show that depletion of GDF6 (BMP13) resulted in a reduction in eye size, loss of laminar structure and a reduction in differentiated neural cell types within the retina. This correlated with a reduction in staining for Smad1/5/8 phosphorylation indicating a decrease in GDF6 signalling through loss of phosphorylation of these intracellular mediators of bone morphogenetic protein (BMP) signalling. In addition, the Pax6 expression domain is reduced in size at early optic vesicle stages. Neural cell adhesion molecule (NCAM) is generally reduced in intensity along the neural tube, while in the retina and brain discreet patches of NCAM expression are also lost. GDF6 knock down resulted in an increase in cell death along the neural tube and within the retina as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining., Conclusion: Our data demonstrate that GDF6 has an important role in neural differentiation in the eye as well as within the central nervous system, and that GDF6 may act in some way to maintain cell survival within the ectoderm, during the normal waves of programmed cell death.

Published
2006
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