The genetic hierarchy that controls gastrulation in Drosophila

In most vertebrates, the upper digestive tract is composed of muscularized jaws linked to the esophagus that permits food ingestion and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to MET/HGF signaling for antero-posterior migration of esophagus muscle progenitors, where Hgf ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulates esophagus myogenesis and identify distinct genetic signatures that can be used as framework to interpret pathologies arising within CPM derivatives.

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A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly activates Myf5 in muscle progenitor cells in the limb

Genes & Development ◽

10.1101/gad.382806 ◽

2006 ◽

Vol 20 (17) ◽

pp. 2450-2464 ◽

Cited By ~ 168

Author(s):

L. Bajard

Keyword(s):

Progenitor Cells ◽

Muscle Progenitor Cells ◽

Genetic Hierarchy

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Mox2 is a component of the genetic hierarchy controlling limb muscle development

Nature ◽

10.1038/21892 ◽

1999 ◽

Vol 400 (6739) ◽

pp. 69-73 ◽

Cited By ~ 97

Author(s):

Baljinder S. Mankoo ◽

Nina S. Collins ◽

Peter Ashby ◽

Elena Grigorieva ◽

Larysa H. Pevny ◽

...

Keyword(s):

Muscle Development ◽

Limb Muscle ◽

Genetic Hierarchy

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Dishevelled is a component of the frizzled signaling pathway in Drosophila

Development ◽

10.1242/dev.121.12.4095 ◽

1995 ◽

Vol 121 (12) ◽

pp. 4095-4102 ◽

Cited By ~ 28

Author(s):

R.E. Krasnow ◽

L.L. Wong ◽

P.N. Adler

Keyword(s):

Signal Transduction ◽

Cell Polarity ◽

Signal Transduction Pathway ◽

Receptor Complex ◽

Transduction Pathway ◽

General Role ◽

Tissue Polarity ◽

Developmental Patterning ◽

Single Process ◽

Genetic Hierarchy

The tissue polarity genes in Drosophila are required to coordinate cell polarity within the plane of the epidermis. Evidence to date suggests that these genes may encode components of a novel signal transduction pathway. Three of the genes, frizzled (fz), dishevelled (dsh), and prickle (pk) share a similar tissue polarity phenotype, suggesting that they function together in a single process. dsh is also known to function as a mediator of wingless (wg) signaling in a variety of developmental patterning processes in the fly. In this study, we make use of a fz transgene and a hypomorphic fz allele as genetic tools in an attempt to order these genes in a genetic hierarchy. Our results argue that dsh encodes a dosage sensitive component required for fz function and that it likely acts downstream of fz in the generation of tissue polarity. Our findings suggest that dsh may have a general role in signal transduction, perhaps as a component of a receptor complex.

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Aggrephagy: lessons from C. elegans

Biochemical Journal ◽

10.1042/bj20121721 ◽

2013 ◽

Vol 452 (3) ◽

pp. 381-390 ◽

Cited By ~ 20

Author(s):

Qun Lu ◽

Fan Wu ◽

Hong Zhang

Keyword(s):

Genetic Model ◽

Protein Aggregates ◽

Degradation Process ◽

Genetic Screens ◽

Concerted Action ◽

C Elegans ◽

Atg Proteins ◽

Higher Eukaryotes ◽

Yeast Genetic ◽

Genetic Hierarchy

Autophagy is a lysosome-mediated degradation process that involves the formation of an enclosed double-membrane autophagosome. Yeast genetic screens have laid the groundwork for a molecular understanding of autophagy. The process, however, exhibits fundamental differences between yeast and higher eukaryotes. Very little is known about essential autophagy components specific to higher eukaryotes. Recent studies have shown that a variety of protein aggregates are selectively removed by autophagy (a process termed aggrephagy) during Caenorhabditis elegans embryogenesis, establishing C. elegans as a multicellular genetic model to delineate the autophagic machinery. The genetic screens were carried out in C. elegans to identify essential autophagy genes. In addition to conserved and divergent homologues of yeast Atg proteins, several autophagy genes conserved in higher eukaryotes, but absent from yeast, were isolated. The genetic hierarchy of autophagy genes in the degradation of protein aggregates in C. elegans provides a framework for understanding the concerted action of autophagy genes in the aggrephagy pathway.

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Muscle LIM Proteins Are Associated with Muscle Sarcomeres and Require dMEF2 for Their Expression during DrosophilaMyogenesis

Molecular Biology of the Cell ◽

10.1091/mbc.10.7.2329 ◽

1999 ◽

Vol 10 (7) ◽

pp. 2329-2342 ◽

Cited By ~ 38

Author(s):

Beth E. Stronach ◽

Patricia J. Renfranz ◽

Brenda Lilly ◽

Mary C. Beckerle

Keyword(s):

Muscle Development ◽

Target Genes ◽

Striated Muscle ◽

Myogenic Differentiation ◽

Muscle Differentiation ◽

Epistasis Analysis ◽

Lim Proteins ◽

Muscle Lim Proteins ◽

Genetic Hierarchy

A genetic hierarchy of interactions, involving myogenic regulatory factors of the MyoD and myocyte enhancer-binding 2 (MEF2) families, serves to elaborate and maintain the differentiated muscle phenotype through transcriptional regulation of muscle-specific target genes. Much work suggests that members of the cysteine-rich protein (CRP) family of LIM domain proteins also play a role in muscle differentiation; however, the specific functions of CRPs in this process remain undefined. Previously, we characterized two members of the Drosophila CRP family, the muscle LIM proteins Mlp60A and Mlp84B, which show restricted expression in differentiating muscle lineages. To extend our analysis ofDrosophila Mlps, we characterized the expression of Mlps in mutant backgrounds that disrupt specific aspects of muscle development. We show a genetic requirement for the transcription factor dMEF2 in regulating Mlp expression and an ability of dMEF2 to bind, in vitro, to consensus MEF2 sites derived from those present inMlp genomic sequences. These data suggest that theMlp genes may be direct targets of dMEF2 within the genetic hierarchy controlling muscle differentiation. Mutations that disrupt myoblast fusion fail to affect Mlp expression. In later stages of myogenic differentiation, which are dedicated primarily to assembly of the contractile apparatus, we analyzed the subcellular distribution of Mlp84B in detail. Immunofluorescent studies revealed the localization of Mlp84B to muscle attachment sites and the periphery of Z-bands of striated muscle. Analysis of mutations that affect expression of integrins and α-actinin, key components of these structures, also failed to perturb Mlp84B distribution. In conclusion, we have used molecular epistasis analysis to position Mlp function downstream of events involving mesoderm specification and patterning and concomitant with terminal muscle differentiation. Furthermore, our results are consistent with a structural role for Mlps as components of muscle cytoarchitecture.

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Author response: A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

10.7554/elife.47460.024 ◽

2019 ◽

Cited By ~ 1

Author(s):

Glenda Comai ◽

Eglantine Heude ◽

Sebastian Mella ◽

Sylvain Paisant ◽

Francesca Pala ◽

...

Keyword(s):

Striated Muscle ◽

Author Response ◽

Genetic Hierarchy

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A distinct cardiopharyngeal mesoderm genetic hierarchy establishes antero-posterior patterning of esophagus striated muscle

10.1101/600841 ◽

2019 ◽

Author(s):

Glenda Comai ◽

Églantine Heude ◽

Sebastien Mella ◽

Sylvain Paisant ◽

Francesca Pala ◽

...

Keyword(s):

Skeletal Muscle ◽

Smooth Muscle ◽

Striated Muscle ◽

Striated Muscles ◽

Loss Of Function ◽

Pharmacological Studies ◽

Posterior Migration ◽

Functional Relevance ◽

Genetic Signatures ◽

Genetic Hierarchy

SUMMARYIn most vertebrates, the upper digestive tract is composed of muscularised jaws linked to the esophagus that permit food uptake and swallowing. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies point to Met/HGF signalling for antero-posterior migration of esophagus muscle progenitors, where HGF ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulate esophagus myogenesis and identify distinct genetic signatures that can be used as a framework to interpret pathologies arising within CPM derivatives.

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Analysis of the genetic hierarchy guiding wing vein development in Drosophila

Development ◽

10.1242/dev.121.3.785 ◽

1995 ◽

Vol 121 (3) ◽

pp. 785-801 ◽

Cited By ~ 26

Author(s):

M.A. Sturtevant ◽

E. Bier

Keyword(s):

Small Group ◽

Genetic Interactions ◽

R Genes ◽

Longitudinal Vein ◽

Wing Vein ◽

Pupal Development ◽

Sequential Model ◽

Vein Formation ◽

Wing Veins ◽

Genetic Hierarchy

The Drosophila rhomboid (rho) and Egf-r genes are members of a small group of genes required for the differentiation of various specific embryonic and adult structures. During larval and early pupal development expression of rho in longitudinal vein primordia mediates the localized formation of wing veins. In this paper we investigate the genetic hierarchy guiding vein development, by testing for genetic interactions between rho alleles and a wide variety of wing vein mutations and by examining the pattern of rho expression in mutant developing wing primordia. We identify a small group of wing vein mutants that interact strongly with rho. Examination of rho expression in these and other key vein mutants reveals when vein development first becomes abnormal. Based on these data and on previous genetic analyses of vein formation we present a sequential model for establishment and differentiation of wing veins.

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