Modular long-range regulation of Myf5 reveals unexpected heterogeneity between skeletal muscles in the mouse embryo

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4455-4467 ◽  
Author(s):  
J. Hadchouel ◽  
S. Tajbakhsh ◽  
M. Primig ◽  
T.H. Chang ◽  
P. Daubas ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Transgene Expression ◽  
Distal Region ◽  
Trunk Muscles ◽  
Regulatory Sequences ◽  
Spatiotemporal Expression ◽  
Branchial Arches ◽  
Early Expression ◽  
Myogenic Factor ◽  
The Brain

The myogenic factor Myf5 plays a key role in muscle cell determination, in response to signalling cascades that lead to the specification of muscle progenitor cells. We have adopted a YAC transgenic approach to identify regulatory sequences that direct the complex spatiotemporal expression of this gene during myogenesis in the mouse embryo. Important regulatory regions with distinct properties are distributed over 96 kb upstream of the Myf5 gene. The proximal 23 kb region directs early expression in the branchial arches, epaxial dermomyotome and in a central part of the myotome, the epaxial intercalated domain. Robust expression at most sites in the embryo where skeletal muscle forms depends on an enhancer-like sequence located between −58 and −48 kb from the Myf5 gene. This element is active in the epaxial and hypaxial myotome, in limb muscles, in the hypoglossal chord and also at the sites of Myf5 transcription in prosomeres p1 and p4 of the brain. However later expression of Myf5 depends on a more distal region between −96 and −63 kb, which does not behave as an enhancer. This element is necessary for expression in head muscles but strikingly only plays a role in a subset of trunk muscles, notably the hypaxially derived ventral body muscles and also those of the diaphragm and tongue. Transgene expression in limb muscle masses is not affected by removal of the −96/-63 region. Epaxially derived muscles and some hypaxial muscles, such as the intercostals and those of the limb girdles, are also unaffected. This region therefore reveals unexpected heterogeneity between muscle masses, which may be related to different facets of myogenesis at these sites. Such regulatory heterogeneity may underlie the observed restriction of myopathies to particular muscle subgroups.

scholarly journals Stability of Lentiviral Vector-Mediated Transgene Expression in the Brain in the Presence of Systemic Antivector Immune Responses

2005 ◽  
Vol 16 (6) ◽  
pp. 741-751 ◽  
Author(s):  
Evelyn Abordo-Adesida ◽  
Antonia Follenzi ◽  
Carlos Barcia ◽  
Sandra Sciascia ◽  
Maria G. Castro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Transgene Expression ◽  
Lentiviral Vector ◽  
The Brain

Role of the neural crest in development of the trabeculae and branchial arches in embryonic sea lamprey, Petromyzon marinus (L)

Development ◽  
1988 ◽  
Vol 102 (2) ◽  
pp. 301-310 ◽  
Author(s):  
R.M. Langille ◽  
B.K. Hall
Keyword(s):  
Neural Crest ◽  
Skeletal Development ◽  
Petromyzon Marinus ◽  
Branchial Arches ◽  
Artificial Fertilization ◽  
Vertebrate Skeleton ◽  
The Brain ◽  
Head Skeleton ◽  
Neurula Stage

Lamprey embryos were obtained by artificial fertilization to ascertain the contributions made by the neural crest to the head skeleton. Early-neurula-stage embryos of Petromyzon marinus were subjected to neural crest extirpation along the anterior half from one of seven zones, raised to a larval stage at which control larvae exhibit well-developed skeletons and analysed by light microscopy for any abnormalities to the cranial and visceral skeleton. The removal of premigratory neural crest at the level of the anterior prosencephalon (zone I) and at the level of somites 6 to 8 (zone VII) had no effect on skeletal development. However, the extirpation of neural crest from the intervening regions was positively correlated with deletions/reductions to the trabeculae (basicranial elements) and to the branchial arches (viscerocranial elements). Alterations to the trabeculae (16/27 cases, or 59%) occurred only after extirpation of zones II-V (corresponding to the posterior prosencephalon to midrhombencephalon) while alterations to the branchial arches (21/28 cases, or 75%) occurred only after removal of neural crest from zones III-VI (corresponding to the mesencephalon to the level of the fifth somite). Furthermore, the first three branchial arches were correlated in a majority of cases with neural crest from zone III, the next two arches with zones IV, V and VI and the last two arches with zone VI. Organs that develop within or adjacent to the area of neural crest extirpation such as the brain, notochord and lateral mesodermal derivatives were not affected. Parachordals were never altered by the operations nor were there any discernible changes to developing mucocartilage or to the prechondrogenic otic capsule. The contributions of the neural crest to the petromyzonid head skeleton described herein are compared with the roles of neural crest in the development of cranial and visceral skeletal elements in other vertebrates. The importance of these findings to the current hypothesis of the phylogeny of the vertebrate skeleton and the central role of the neural crest in vertebrate cephalization is discussed.

Jaw and branchial arch mutants in zebrafish I: branchial arches

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 329-344 ◽  
Author(s):  
T.F. Schilling ◽  
T. Piotrowski ◽  
H. Grandel ◽  
M. Brand ◽  
C.P. Heisenberg ◽  
...  
Keyword(s):  
Neural Crest ◽  
Zebrafish Embryo ◽  
Neural Crest Cells ◽  
Branchial Arch ◽  
Pigment Cells ◽  
Pharyngeal Arches ◽  
Pectoral Fins ◽  
Branchial Arches ◽  
Group Members ◽  
The Brain

Jaws and branchial arches together are a basic, segmented feature of the vertebrate head. Seven arches develop in the zebrafish embryo (Danio rerio), derived largely from neural crest cells that form the cartilaginous skeleton. In this and the following paper we describe the phenotypes of 109 arch mutants, focusing here on three classes that affect the posterior pharyngeal arches, including the hyoid and five gill-bearing arches. In lockjaw, the hyoid arch is strongly reduced and subsets of branchial arches do not develop. Mutants of a large second class, designated the flathead group, lack several adjacent branchial arches and their associated cartilages. Five alleles at the flathead locus all lead to larvae that lack arches 4–6. Among 34 other flathead group members complementation tests are incomplete, but at least six unique phenotypes can be distinguished. These all delete continuous stretches of adjacent branchial arches and unpaired cartilages in the ventral midline. Many show cell death in the midbrain, from which some neural crest precursors of the arches originate. lockjaw and a few mutants in the flathead group, including pistachio, affect both jaw cartilage and pigmentation, reflecting essential functions of these genes in at least two neural crest lineages. Mutants of a third class, including boxer, dackel and pincher, affect pectoral fins and axonal trajectories in the brain, as well as the arches. Their skeletal phenotypes suggest that they disrupt cartilage morphogenesis in all arches. Our results suggest that there are sets of genes that: (1) specify neural crest cells in groups of adjacent head segments, and (2) function in common genetic pathways in a variety of tissues including the brain, pectoral fins and pigment cells as well as pharyngeal arches.

DARPP-32 promoter directs transgene expression to renal thick ascending limb of loop of Henle

1995 ◽  
Vol 269 (4) ◽  
pp. F564-F570 ◽  
Author(s):  
S. Blau ◽  
L. Daly ◽  
A. Fienberg ◽  
G. Teitelman ◽  
M. E. Ehrlich
Keyword(s):  
Transgene Expression ◽  
Ectopic Expression ◽  
Medium Size ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Transcription Start Sites ◽  
Medullary Thick Ascending Limb ◽  
Spiny Neurons ◽  
Adult Kidney ◽  
The Brain

DARPP-32, a dopamine- and adenosine 3',5'-cyclic monophosphate (cAMP)-regulated inhibitor of protein phosphatase-1, is highly colocalized with neuronal and nonneuronal D1-type receptors. DARPP-32 concentration is enriched in the renal outer medulla and in the medium-size spiny neurons of the brain. In the ascending limb of the loop of Henle, DARPP-32 is phosphorylated following stimulation by dopamine and other first messengers, and in this form inhibits the activity of the Na(+)-K(+)-adenosinetriphosphatase pump. For functional analysis of the DARPP-32 promoter in the kidney, we characterized the murine gene. There are two groups of transcription start sites utilized in the brain, but the proximal set appears to be preferentially used in the kidney. In four of four lines of mice carrying a DARPP-32/lacZ transgene with 2.1 kb of 5'-flanking DNA, adult kidney lacZ transgene expression mimicked that of endogenous DARPP-32. There was no ectopic expression in peripheral organs. We conclude that the sequences necessary for direction of DARPP-32 expression to the medullary thick ascending limb are contained within this 2.1-kb fragment.

beta-MHC transgene expression in suspended and mechanically overloaded/suspended soleus muscle of transgenic mice

1997 ◽  
Vol 272 (5) ◽  
pp. R1552-R1561 ◽  
Author(s):  
J. J. McCarthy ◽  
A. M. Fox ◽  
G. L. Tsika ◽  
L. Gao ◽  
R. W. Tsika
Keyword(s):  
Transgenic Mice ◽  
Soleus Muscle ◽  
Transgene Expression ◽  
Specific Activity ◽  
Fiber Type ◽  
Weight Bearing ◽  
Troponin C ◽  
Hindlimb Suspension ◽  
Regulatory Sequences ◽  
Type I

Non-weight-bearing (NWB) activity [space flight and hindlimb suspension (HS)] results in the loss of soleus muscle mass, a slow-to-fast fiber-type conversion, and decreased beta-myosin heavy chain (beta-MHC) protein and mRNA expression. To identify beta-MHC promoter sequences required for decreased beta-MHC expression in response to HS, we have modified an existing noninvasive hindlimb unweighting model to accommodate the use of (transgenic) mice. After 2 wk of HS, body and muscle (soleus > gastrocnemius > plantaris) weights were decreased as was the proportion of histochemically classified type I fibers in HS soleus muscle. Northern blot analysis revealed decreases in endogenous mRNA representing beta-MHC, slow myosin light chain 1 and 2, and cardiac/slow troponin C, whereas those representing skeletal troponin C, muscle creatine kinase, and glyceraldehyde-3-phosphate dehydrogenase increased. Protein extracts prepared from HS soleus (SS) muscle of mice harboring transgenes comprised of 5.6 or 0.6 kilobase of wild type (wt) mouse beta-MHC promoter (beta 5.6 wt, beta 0.6wt) and those carrying the simultaneous mutation (mut) of the MCAT, C-rich, and beta e3 subregions (beta 5.6mut3, beta 0.6mut3) revealed decreases in chloramphenicol acetyltransferase (CAT) specific activity relative to respective controls. Decreased CAT mRNA was observed for transgene beta 5.6mut3, line 85. Two weeks of the simultaneous imposition of mechanical overload (synergist ablation) and HS (MOV/HS) countermanded the loss in absolute and normalized SS weight but did not decrease beta 0.6wt transgene expression. These transgenic results demonstrate that regulatory sequences within a 600-base pair beta-MHC promoter are sufficient to direct decreased transcription of beta-MHC transgenes after 2 wk of HS.

scholarly journals E-box sites and a proximal regulatory region of the muscle creatine kinase gene differentially regulate expression in diverse skeletal muscles and cardiac muscle of transgenic mice.

1996 ◽  
Vol 16 (9) ◽  
pp. 5058-5068 ◽  
Author(s):  
M A Shield ◽  
H S Haugen ◽  
C H Clegg ◽  
S D Hauschka
Keyword(s):  
Creatine Kinase ◽  
Skeletal Muscles ◽  
Transgene Expression ◽  
Regulatory Region ◽  
Regulatory Sequences ◽  
Striated Muscles ◽  
Muscle Creatine Kinase ◽  
E Box ◽  
Muscle Creatine ◽  
E Boxes

Previous analysis of the muscle creatine kinase (MCK) gene indicated that control elements required for transcription in adult mouse muscle differed from those required in cell culture, suggesting that distinct modes of muscle gene regulation occur in vivo. To examine this further, we measured the activity of MCK transgenes containing E-box and promoter deletions in a variety of striated muscles. Simultaneous mutation of three E boxes in the 1,256-bp MCK 5' region, which abolished transcription in muscle cultures, had strikingly different effects in mice. The mutations abolished transgene expression in cardiac and tongue muscle and caused a reduction in expression in the soleus muscle (a muscle with many slow fibers) but did not affect expression in predominantly fast muscles: quadriceps, abdominals, and extensor digitorum longus. Other regulatory sequences with muscle-type-specific activities were found within the 358-bp 5'-flanking region. This proximal region conferred relatively strong expression in limb and abdominal skeletal muscles but was inactive in cardiac and tongue muscles. However, when the 206-bp 5' enhancer was ligated to the 358-bp region, high levels of tissue-specific expression were restored in all muscle types. These results indicate that E boxes and a proximal regulatory region are differentially required for maximal MCK transgene expression in different striated muscles. The overall results also imply that within skeletal muscles, the steady-state expression of the MCK gene and possibly other muscle genes depends on transcriptional mechanisms that differ between fast and slow fibers as well as between the anatomical and physiological attributes of each specific muscle.

scholarly journals Restricted Transgene Expression in the Brain with Cell-Type Specific Neuronal Promoters

2012 ◽  
Vol 23 (4) ◽  
pp. 242-254 ◽  
Author(s):  
Aurélie Delzor ◽  
Noelle Dufour ◽  
Fanny Petit ◽  
Martine Guillermier ◽  
Diane Houitte ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Cell Type ◽  
Cell Type Specific ◽  
The Brain

Spatiotemporal expression of retrogene–host pair Mcts2/H13 in mouse embryo, and Mcts2 has no influence on H13 transcription pattern in NIH/3T3 cells

2014 ◽  
Vol 116 (2) ◽  
pp. 312-318 ◽  
Author(s):  
Zhijun Huang ◽  
Zhengbin Han ◽  
Fengwei Zhang ◽  
Hongjuan He ◽  
Shihuan Yu ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
3T3 Cells ◽  
Transcription Pattern ◽  
Spatiotemporal Expression ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Infectious delivery and long-term persistence of transgene expression in the brain by a 135-kb iBAC-FXN genomic DNA expression vector

Gene Therapy ◽  
2011 ◽  
Vol 18 (10) ◽  
pp. 1015-1019 ◽  
Author(s):  
A Gimenez-Cassina ◽  
R Wade-Martins ◽  
S Gomez-Sebastian ◽  
J-C Corona ◽  
F Lim ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Transgene Expression ◽  
Expression Vector ◽  
The Brain
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