Analysis of Mouse Development with Conditional Mutagenesis

Lewandoski, Mark

doi:10.1007/978-3-540-35109-2_10

Cited by 17 publications

(8 citation statements)

References 158 publications

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“…The extent of intrinsic and extrinsic contribution during lineage progression from the most ancestral cell to a differentiated muscle fiber will vary depending on the respective stage of cellular commitment but are unlikely to be exclusive. The molecular mechanisms that integrate various environmental and inherent controls to establish the character of cells in the myogenic lineage are a matter of intense research, and the recent emergence of powerful tools in mouse genetics has provided significant new insights (Lewandoski 2007). The following sections review our current understanding of the molecular regulation of muscle formation during development and in the adult.…”

Section: Introductionmentioning

confidence: 99%

Building Muscle: Molecular Regulation of Myogenesis

Bentzinger¹,

Wang²,

Rudnicki³

2012

Cold Spring Harbor Perspectives in Biology

925

878

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SUMMARYThe genesis of skeletal muscle during embryonic development and postnatal life serves as a paradigm for stem and progenitor cell maintenance, lineage specification, and terminal differentiation. An elaborate interplay of extrinsic and intrinsic regulatory mechanisms controls myogenesis at all stages of development. Many aspects of adult myogenesis resemble or reiterate embryonic morphogenetic episodes, and related signaling mechanisms control the genetic networks that determine cell fate during these processes. An integrative view of all aspects of myogenesis is imperative for a comprehensive understanding of muscle formation. This article provides a holistic overview of the different stages and modes of myogenesis with an emphasis on the underlying signals, molecular switches, and genetic networks.

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Section: Introductionmentioning

confidence: 99%

Building Muscle: Molecular Regulation of Myogenesis

Bentzinger¹,

Wang²,

Rudnicki³

2012

Cold Spring Harbor Perspectives in Biology

925

878

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“…The presence of Neo in targeting constructs is known to interfere with gene expression (Lewandoski, ). Consistent with this, viable Adamts9 fl‐Neo / fl‐Neo mice were not obtained from intercrosses of Adamts9 fl‐Neo /+ mice.…”

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confidence: 97%

A new Adamts9 conditional mouse allele identifies its non‐redundant role in interdigital web regression

Dubail

Aramaki-Hattori

Bader

et al. 2014

Genesis

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ADAMTS9 is the most conserved member of a large family of secreted metalloproteases having diverse functions. Adamts9 null mice die before gastrulation, precluding investigations of its roles later in embryogenesis, in adult mice or disease models. We therefore generated a floxed Adamts9 allele to bypass embryonic lethality. In this mutant, unidirectional loxP sites flank exons 5 through 8, which encode the catalytic domain, including the protease active site. Mice homozygous for the floxed allele were viable, lacked an overt phenotype, and were fertile. Conversely, mice homozygous for a germ-line deletion produced from the floxed allele by Cre-lox recombination did not survive past gastrulation. Hemizygosity of the deleted Adamts9 in combination with mutant Adamts20 led to cleft palate and severe white spotting as previously described. Previously, Adamts9 haploinsufficiency combined with either Adamts20 or Adamts5 nullizygosity suggested a cooperative role in interdigital web regression, but the outcome of deletion of Adamts9 alone remained unknown. Here, Adamts9 was conditionally deleted in limb mesoderm using Prx1-Cre mice. Unlike other ADAMTS single knockouts, limb-specific Adamts9 deletion resulted in soft-tissue syndactyly (STS) with 100% penetrance and concurrent deletion of Adamts5 increased the severity of STS. Thus, Adamts9 has both non-redundant and cooperative roles in ensuring interdigital web regression. This new allele will be useful for investigating other biological functions of ADAMTS9.

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“…Future studies involving segment-or cell-specific gene inactivation by in vivo strategies (Gao and Zhang, 2007;Glaser et al, 2005;Kuhn et al, 2007;Lewandoski, 2007;Prawitt et al, 2004;Ristevski, 2005;Xia et al, 2006) should provide accurate knowledge on how various growth factor signaling pathways are coupled to regulate cell cycle control in the epididymis. Our studies provide expression evaluation of D-type cyclins as a potential biological endpoint for assessment of physical injury or exposure to various reproductive toxicants that often lead to changes in cell cycle events in the epididymis.…”

Section: Discussionmentioning

confidence: 99%

Segment- And Cell-Specific Expression of Dtype Cyclins in the Postnatal Mouse Epididymis

Wang

2007

Biology of Reproduction

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Sperm transport, maturation and storage are the essential functions of the epididymis. The epididymis in the mouse is structurally characterized by regional and segmental organization including caput, corpus and cauda epididymis that are comprised of ten segments. Although several growth factor signaling pathways have been discovered in the epididymis, how these converge onto the cell cycle components is unknown. To begin to elucidate the growth factor control of cell cycle events in the epididymis, we analyzed the expression of D-type cyclins at different postnatal ages. At 7d, cyclin D1 was mainly expressed in the cauda epithelium, by 14d its expression occurred in the epithelium of caput, corpus and cauda that persisted up to 21d. By 42d, cyclin D1 was mostly detectable in the principal cells of the caput and corpus (segments 1-7) but not in the cauda epididymis. Expression of cyclin D2, unlike that of cyclin D1, was evident only at 42d but not earlier, and was mostly confined to corpus and cauda epithelium. In contrast to both cyclin D1 and D2, cyclin D3 was expressed primarily in the interstitium at 7d and by 21d its expression was localized to the epithelium of the corpus and cauda epididymis. By 42d, expression of cyclin D3 peaked in segments 6-10 and confined to basal and principal cells of the corpus and apical cells of the cauda epithelium. Ki67 immunoreactivity confirmed absence of cell proliferation despite continued expression of D-type cyclins in the adult epididymis. Collectively, on the basis of our immunophenotyping and protein expression data, we conclude that the D-type cyclins are expressed in a development -, segment-, and cell-specific manner in the postnatal mouse epididymis.

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Analysis of Mouse Development with Conditional Mutagenesis

Cited by 17 publications

References 158 publications

Building Muscle: Molecular Regulation of Myogenesis

Building Muscle: Molecular Regulation of Myogenesis

A new Adamts9 conditional mouse allele identifies its non‐redundant role in interdigital web regression

Segment- And Cell-Specific Expression of Dtype Cyclins in the Postnatal Mouse Epididymis

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