Divergent roles for <i>NK-2</i> class homeobox genes in cardiogenesis in flies and mice

Ranganayakulu, Gogineni; Elliott, David A.; Harvey, Richard P.; Olson, Eric N.

doi:10.1242/dev.125.16.3037

Cited by 176 publications

(26 citation statements)

References 64 publications

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“…These data suggest that NCDN regulation of branching myofibrillar network formation in IF muscles occur between 24 and 48 h APF. Consistently, developmental timecourse analyses of pupal IF muscles lacking NCDN from early myoblast formation through the lifespan ( Mef2-Gal4 47 ) reveal that loss of NCDN leads to myofibrillar defects beginning between 32 and 48 h APF (Fig. 5f–u ).…”

Section: Resultssupporting

confidence: 70%

Regulation of the evolutionarily conserved muscle myofibrillar matrix by cell type dependent and independent mechanisms

et al. 2022

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Skeletal muscles play a central role in human movement through forces transmitted by contraction of the sarcomere. We recently showed that mammalian sarcomeres are connected through frequent branches forming a singular, mesh-like myofibrillar matrix. However, the extent to which myofibrillar connectivity is evolutionarily conserved as well as mechanisms which regulate the specific architecture of sarcomere branching remain unclear. Here, we demonstrate the presence of a myofibrillar matrix in the tubular, but not indirect flight (IF) muscles within Drosophila melanogaster. Moreover, we find that loss of transcription factor H15 increases sarcomere branching frequency in the tubular jump muscles, and we show that sarcomere branching can be turned on in IF muscles by salm-mediated conversion to tubular muscles. Finally, we demonstrate that neurochondrin misexpression results in myofibrillar connectivity in IF muscles without conversion to tubular muscles. These data indicate an evolutionarily conserved myofibrillar matrix regulated by both cell-type dependent and independent mechanisms.

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Section: Resultssupporting

confidence: 70%

Regulation of the evolutionarily conserved muscle myofibrillar matrix by cell type dependent and independent mechanisms

et al. 2022

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“…For genetic experiments, we used the pan‐neural elav‐ GAL4 driver (Luo et al , 1994) and the muscle‐specific Mef2‐ GAL4 driver (Ranganayakulu et al , 1998) as main driver. In addition, we combined these two driver lines ( elav ‐GAL4; Mef2 ‐GAL4 driver) for this study.…”

Section: Methodsmentioning

confidence: 99%

Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos

Gao²,

Sanchez³

et al. 2022

Molecular Systems Biology

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The correct wiring of neuronal circuits is one of the most complex processes in development, since axons form highly specific connections out of a vast number of possibilities. Circuit structure is genetically determined in vertebrates and invertebrates, but the mechanisms guiding each axon to precisely innervate a unique pre‐specified target cell are poorly understood. We investigated Drosophila embryonic motoneurons using single‐cell genomics, imaging, and genetics. We show that a cell‐specific combination of homeodomain transcription factors and downstream immunoglobulin domain proteins is expressed in individual cells and plays an important role in determining cell‐specific connections between differentiated motoneurons and target muscles. We provide genetic evidence for a functional role of five homeodomain transcription factors and four immunoglobulins in the neuromuscular wiring. Knockdown and ectopic expression of these homeodomain transcription factors induces cell‐specific synaptic wiring defects that are partly phenocopied by genetic modulations of their immunoglobulin targets. Taken together, our data suggest that homeodomain transcription factor and immunoglobulin molecule expression could be directly linked and function as a crucial determinant of neuronal circuit structure.

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“…The cardiac transcription factors Gata4, Nkx2-5, and Tbx5 often co-occupy the same enhancers and their activation domains were previously identified (Morrisey et al, 1997;Ranganayakulu et al, 1998;Zaragoza et al, 2004). We used them to create dCas9-Gata4-Nkx2-5-Tbx5 (dCas9-GNT) endogenously based CRISPRa tool (Fig.…”

Section: Recruitment Of Endogenous Transcription Factor Activation Do...mentioning

confidence: 99%

Recruitment of transcriptional effectors by Cas9 creates cis regulatory elements and demonstrates distance-dependent transcriptional regulation

Boulos

Ehrlich

Avidan

et al. 2022

Preprint

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It is essential to regulate the expression of genes, such as those encoding the proteins of the cardiac sarcomere. This regulation is often mediated by cis regulatory elements termed enhancers and repressors that recruit transcription factors to gene-distal sites. However, the relationship between transcription factors recruitment to gene-distant sites and the regulation of gene expression is not fully understood. Specifically, it is unclear if such recruitment to any genomic site is sufficient to form an enhancer or repressor at the site, and what is the relationship between the cis regulatory element’s position and its ability to control the transcription of distant genes. Using dead Cas9 to recruit either viral or endogenous transcription factor activation domains, we demonstrate that targeting ‘naïve’ genomic sites lacking open chromatin or active enhancer marks is sufficient to alter the chromatin signature of the target site, the distant gene promoter, and significantly induce the distant gene expression, even across chromatin insulating loci. The magnitude of induction is affected by the distance between the activation site and the cognate gene in a non-linear manner. Dead Cas9 mediated recruitment of repression domains behave similarly to activation in that targeting of non-regulatory regions could repress gene expression with a nonlinear distance dependence and across chromatin insulating loci. These findings expand the models of enhancer generation and function by showing that an arbitrary genomic site can become a regulatory element and interact epigenetically and transcriptionally with a distant promoter. They also provide new fundamental insights into the rules governing gene expression.

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Divergent roles for NK-2 class homeobox genes in cardiogenesis in flies and mice

Cited by 176 publications

References 64 publications

Regulation of the evolutionarily conserved muscle myofibrillar matrix by cell type dependent and independent mechanisms

Regulation of the evolutionarily conserved muscle myofibrillar matrix by cell type dependent and independent mechanisms

Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos

Recruitment of transcriptional effectors by Cas9 creates cis regulatory elements and demonstrates distance-dependent transcriptional regulation

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