Structural and experimental investigations of the functional anatomy and the turgor of the notochord in the larval tail of anuran tadpoles

Platz, Franz

doi:10.1016/j.aanat.2006.01.009

Cited by 13 publications

(25 citation statements)

References 27 publications

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“…Although scientific efforts have primarily focused on embryonic development, the significance of notochordal cells likely extends even beyond morphogenesis of the spine. The immature NP derives its mechanical and biological function from these cells (Adams et al, 1990;Platz, 2006), and understanding their regulation by environmental variables will provide insight into aging, disease, and potentially repair. Evidence suggests that discogenic spinal disorders may be linked with changes in the NP's abilities to sustain a high internal turgor pressure, maintain flexibility, and provide proper IVD load distribution.…”

Section: Discussionmentioning

confidence: 99%

Environmental regulation of notochordal gene expression in nucleus pulposus cells

Rastogi

Thakore

Leung

et al. 2009

Journal Cellular Physiology

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Cells of the nucleus pulposus (NP) in the intervertebral disc are derived directly from the embryonic notochord. In humans, a shift in NP cell population coincides with the beginning of age-related changes in the extracellular matrix that can lead to spinal disorders. To begin identifying the bases of these changes, the manner by which relevant environmental factors impact cell function must be understood. This study investigated the roles of biochemical, nutritional, and physical factors in regulating immature NP cells. Specifically, we examined cell morphology, attachment, proliferation, and expression of genes associated with the notochord and immature NP (Sox9, CD24, and type IIA procollagen). Primary cells isolated from rat caudal discs were exposed to different media formulations and physical culture configurations either in 21% (ambient) or 2% (hypoxic) O2. As expected, cells in alginate beads retained a vacuolated morphology similar to chordocytes, with little change in gene expression. Interestingly, NP tissues not enzymatically digested were more profoundly influenced by oxygen. In monolayer, alpha-MEM preserved vacuolated morphology, produced the highest efficiency of attachment, and best maintained gene expression. DMEM and Opti-MEM cultures resulted in high levels of proliferation, but these appeared to involve small non-vacuolated cells. Gene expression patterns for cells in DMEM monolayer cultures were consistent with chondrocyte de-differentiation, with the response being delayed by hypoxia. Overall, results indicate that certain environmental conditions induce cellular changes that compromise the notochordal phenotype in immature NP. These results form the foundation on which the mechanisms of such changes can be elucidated.

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Section: Discussionmentioning

confidence: 99%

Environmental regulation of notochordal gene expression in nucleus pulposus cells

Rastogi

Thakore

Leung

et al. 2009

Journal Cellular Physiology

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“…While largely considered only as a transient signaling structure, the notochord also serves as a primitive axial support structure (Stemple, 2005), possibly by acting as a hydrostatic skeleton. There is evidence that the interior of the notochord is pressurized with its integrity maintained by the proteoglycan (PG)- and laminin-rich sheath (Platz, 2006). During embryonic morphogenesis, the notochord is pinched off by the formation of vertebral bodies (Aszodi, et al, 1998, Grotmol, et al, 2003).…”

Section: Nucleus Pulposusmentioning

confidence: 99%

Cellular mechanobiology of the intervertebral disc: New directions and approaches

Hsieh

Twomey

2010

Journal of Biomechanics

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The more we learn about the intervertebral disc (IVD), the more we come to appreciate the intricacies involved in transmission of forces through the ECM to the cell, and in the biological determinants of its response to mechanical stress. This review highlights recent developments in our knowledge of IVD physiology and examines their impact on cellular mechanobiology. Discussion centers around the continually evolving cellular and microstructural anatomy of the nucleus pulposus (NP) and the annulus fibrosus (AF) in response to complex stresses generated in support of axial load and spinal motion. Particular attention has been given to cells from the immature NP and the interlamellar AF, and assessment of their potential mechanobiologic contributions to the health and function of the IVD. In addition, several innovative approaches that have been brought to bear on studying the interplay between disc cells and their micromechanical environment are discussed. Techniques for “engineering” cellular function and technologies for fabricating more structurally defined biomaterial scaffolds have recently been employed in disc research. Such tools can be used to elucidate the biological and physical mechanisms by which different IVD cell populations are regulated by mechanical stress, and contribute to advancement of preventative and therapeutic measures.

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“…Fibrillar collagen is a main component of the vertebrate notochordal sheath ( e.g ., Grotmol et al, 2006; Platz, 2006) and mutations in genes encoding collagen-modifying enzymes, such as the lysyl oxidases, have been shown to compromise the integrity of this structure causing notochord distortions (Anderson et al, 2007; Gansner et al, 2007). Similarly, our group has shown that two lysyl oxidases are expressed in the Ciona notochord and/or its precursors (Kugler et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

The evolutionarily conserved leprecan gene: Its regulation by Brachyury and its role in the developing Ciona notochord

Dunn

Gregorio

2009

Developmental Biology

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In Ciona intestinalis, leprecan was identified as a target of the notochord-specific transcription factor Ciona Brachyury (Ci-Bra) (Takahashi et al., 1999). By screening ~14 kb of the Ci-leprecan locus for cis-regulatory activity, we have identified a 581-bp minimal notochord-specific cis-regulatory module (CRM) whose activity depends upon T-box binding sites located at the 3’-end of its sequence. These sites are specifically bound in vitro by a GST-Ci-Bra fusion protein, and mutations that abolish binding in vitro result in loss or decrease of regulatory activity in vivo. Serial deletions of the 581-bp notochord CRM revealed that this sequence is also able to direct expression in muscle cells through the same T-box sites that are utilized by Ci-Bra in the notochord, which are also bound in vitro by the muscle-specific T-box activators Ci-Tbx6b and Ci-Tbx6c. Additionally, we created plasmids aimed to interfere with the function of Ci-leprecan and categorized the resulting phenotypes, which consist of variable dislocations of notochord cells along the anterior-posterior axis. Together, these observations provide mechanistic insights generally applicable to T-box transcription factors and their target sequences, as well as a first set of clues on the function of Leprecan in early chordate development.

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Structural and experimental investigations of the functional anatomy and the turgor of the notochord in the larval tail of anuran tadpoles

Cited by 13 publications

References 27 publications

Environmental regulation of notochordal gene expression in nucleus pulposus cells

Environmental regulation of notochordal gene expression in nucleus pulposus cells

Cellular mechanobiology of the intervertebral disc: New directions and approaches

The evolutionarily conserved leprecan gene: Its regulation by Brachyury and its role in the developing Ciona notochord

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