ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish

Qu, Xiaomei; Jia, Haibo; Garrity, Deborah M.; Tompkins, Kevin L.; Batts, Lorene; Appel, Bruce; Zhong, Tao; Baldwin, H. Scott

doi:10.1016/j.ydbio.2008.02.044

Cited by 64 publications

(76 citation statements)

References 53 publications

(57 reference statements)

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“…This suggests that these genes are expressed by at least some neurons labelled by the pax2a:GFP transgene and some other post-mitotic neurons. Consistent with this, nrdg4 is expressed broadly in the medial region of the spinal cord in a region that overlaps where Tg(pax2a:GFP) GFP-positive neurons are found (Qu et al, 2008) and tusc3 and coro1b appear to be broadly expressed throughout at least most of the spinal cord (Thisse et al, 2004;www. zfin.org). The expression of wu:fc39d03 and hcn2 is currently unknown.…”

Section: Expression-profiling Using Affymetrix Microarrayssupporting

confidence: 67%

RNA profiling of FAC‐sorted neurons from the developing zebrafish spinal cord

Cerda

Hargrave

Lewis

2008

Developmental Dynamics

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In this report, we describe a successful protocol for isolating and expression-profiling live fluorescentprotein-labelled neurons from zebrafish embryos. As a proof-of-principle for this method, we FAC-sorted and RNA-profiled GFP-labelled spinal CiA interneurons and compared the expression profile of these cells to those of post-mitotic spinal neurons in general and to all trunk cells. We show that RNA of sufficient quality and quantity to uncover both expected and novel transcription profiles via Affymetrix microarray analysis can be extracted from 5,700 to 20,000 FAC-sorted cells. As part of this study, we also further confirm the genetic homology of mammalian and zebrafish V1 interneurons, by demonstrating that zebrafish V1 cells (CiAs) express genes that encode for the transcription factors Lhx1a and Lhx5. This protocol for dissociating, sorting and RNA-profiling neurons from organogenesis-stage zebrafish embryos should also be applicable to other developing organs and tissues and potentially other model organisms. Developmental Dynamics 238:150 -161, 2009.

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Section: Expression-profiling Using Affymetrix Microarrayssupporting

confidence: 67%

RNA profiling of FAC‐sorted neurons from the developing zebrafish spinal cord

Cerda

Hargrave

Lewis

2008

Developmental Dynamics

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“…However, recent reports implicate biological roles of NDRG4 in the heart. The knockdown of NDRG4 during embryonic development in zebrafish results in phenotypes such as a hypoplastic heart with pericardial edema, a dilated atrium, looping defects, reduced circulation, and a slower heart rate with weaker contraction (40). Severe ventricular hypoplasia down-regulates NDRG4 expression in the mouse embryonic heart (16).…”

Section: Discussionmentioning

confidence: 99%

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

Yamamoto

Kokame

Okuda

et al. 2011

Journal of Biological Chemistry

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The N-myc downstream-regulated gene (NDRG) family consists of four related proteins, NDRG1-NDRG4, in mammals. We previously generated NDRG1-deficient mice that were unable to maintain myelin sheaths in peripheral nerves. This condition was consistent with human hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D, caused by a nonsense mutation of NDRG1. In contrast, the effects of genetic defects of the other NDRG members remain unknown. In this study, we focused on NDRG4, which is specifically expressed in the brain and heart. In situ mRNA hybridization on the brain revealed that NDRG4 was expressed in neurons of various areas. We generated NDRG4-deficient mice that were born normally with the expected Mendelian frequency. Immunochemical analysis demonstrated that the cortex of the NDRG4-deficient mice contained decreased levels of brain-derived neurotrophic factor (BDNF) and normal levels of glial cell line-derived neurotrophic factor, NGF, neurotrophin-3, and TGF-␤1. Consistent with BDNF reduction, NDRG4-deficient mice had impaired spatial learning and memory but normal motor function in the Morris water maze test. When temporary focal ischemia of the brain was induced, the sizes of the infarct lesions were larger, and the neurological deficits were more severe in NDRG4-deficient mice compared with the control mice. These findings indicate that NDRG4 contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress. N-myc downstream-regulated gene (NDRG)3 family members NDRG1-NDRG4 are intracellular proteins, consist of 340 -394 amino acid residues, and share 53-65% sequence identity with each other. Furthermore, accumulating evidence implicates their roles in development, cancer metastasis, and the immune system (1-5).We originally identified RTP (NDRG1) as a homocysteineresponsive gene in human umbilical vein endothelial cells (6), which is also called DRG1, Cap43, Rit42, Ndr1, and PROXY-1. NDRG1 expression is induced by a number of conditions, such as DNA damage, hypoxia, and intracellular calcium ion elevation (4). Overexpression of NDRG1 suppresses the metastatic potency of some types of cancer cells (4) and enhances the degranulation of mast cells in response to various stimuli (7). A nonsense mutation of NDRG1 causes hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D, which presents as distal muscle wasting and atrophy, foot and hand deformities, tendon areflexia, sensory loss, and deafness in afflicted individuals (8). We previously generated NDRG1-deficient mice and revealed the essential role of NDRG1 in the cytoplasm of Schwann cells for the maintenance of myelin sheaths in peripheral nerves (9). A frame shift deletion of Ndrg1 in Greyhounds also causes polyneuropathy (10).Similar to NDRG1, the expression of NDRG2 is induced by stress conditions such as hypoxia (1). NDRG2 expression is upregulated in cort...

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“…In zebrafish, evidence indicates that cardiac growth after looping of the heart tube occurs exclusively via the proliferation of existing cardiomyocytes (de Pater et al, 2009;Jopling et al, 2010;Kikuchi et al, 2011a;Qu et al, 2008). Recently, a cardiomyocyte-specific adaptation of Brainbow technology (Livet et al, 2007) was developed in zebrafish to genetically label cardiomyocytes with dozens of unique colors and follow their contributions throughout life (Gupta and Poss, 2012).…”

Section: Early Cardiogenesismentioning

confidence: 99%

Building and re-building the heart by cardiomyocyte proliferation

2016

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The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most-cited basis of this ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes. However, mammalian cardiomyocytes can avidly proliferate during fetal and neonatal development, and both adult zebrafish and neonatal mice can regenerate cardiac muscle after injury, suggesting that latent regenerative potential exists. Dissecting the cellular and molecular mechanisms that promote cardiomyocyte proliferation throughout life, deciphering why proliferative capacity normally dissipates in adult mammals, and deriving means to boost this capacity are primary goals in cardiovascular research. Here, we review our current understanding of how cardiomyocyte proliferation is regulated during heart development and regeneration.

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ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish

Cited by 64 publications

References 53 publications

RNA profiling of FAC‐sorted neurons from the developing zebrafish spinal cord

RNA profiling of FAC‐sorted neurons from the developing zebrafish spinal cord

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

Building and re-building the heart by cardiomyocyte proliferation

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