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I M McGonnell

Publications and source records attributed to I M McGonnell.

8 recordsLinked to original sources
PubMed2006

Evidence that the canonical Wnt signalling pathway regulates deer antler regeneration.

Wnt signalling regulates many developmental processes, including the fate specification, polarity, migration, and proliferation of cranial neural crest. The canonical Wnt pathway has also been shown to play an important role in bone physiology and there is evidence for its recapitulation during organ regeneration in lower vertebrates. This study explores the role of the Wnt signalling pathway in deer antlers, frontal bone appendages that are the only mammalian organs capable of regeneration. Immunocytochemistry was used to map the distribution of the activated form of beta-catenin ((a)betaCAT). A low level of (a)betaCAT staining was detected in chondrocytes and in osteoblasts at sites of endochondral bone formation. However, (a)betaCAT was localised in cellular periosteum and in osteoblasts in intramembranous bone, where it co-localised with osteocalcin. The most intense (a)betaCAT staining was in dividing undifferentiated cells in the mesenchymal growth zone. Antler progenitor cells (APCs) were cultured from this region and when the canonical Wnt pathway was inhibited at the level of Lef/TCF by epigallocatechin gallate (EGCG), the cell number decreased. TUNEL staining revealed that this was as a result of increased apoptosis. Activation of the pathway by lithium chloride (LiCl) had no effect on cell number but inhibited alkaline phosphate activity (ALP), a marker of APC differentiation, whereas EGCG increased ALP activity. This study demonstrates that beta-catenin plays an important role in the regulation of antler progenitor cell survival and cell fate. It also provides evidence that beta-catenin's function in regulating bone formation by osteoblasts may be site-specific.

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PubMed2006

Fishing for gene function--endocrine modelling in the zebrafish.

The use of zebrafish (Danio rerio) in scientific research is growing rapidly. It initially became popular as a model of vertebrate development because zebrafish embryos develop rapidly and are transparent. In the past 5 years, the sequencing of the zebrafish genome has increased the profile of zebrafish research even further, expanding into other areas such as pharmacology, cancer research and drug discovery. The use of zebrafish in endocrine research has mainly been confined to the study of the development of endocrine organs. However, it is likely to be a useful model in other areas of endocrinology, as there are a wide variety of both forward and reverse genetic techniques that can be employed in the zebrafish to decipher gene function in disease states. In this review, we compare the endocrine system of the zebrafish to mouse and human, demonstrating that the systems are sufficiently similar for zebrafish to be employed as a model for endocrine research. We subsequently review the repertoire of genetic techniques commonly employed in the zebrafish model to understand gene function in vertebrate development and disease. We anticipate that the use of these techniques will make the zebrafish a prominent model in endocrine research in the coming years.

Animals↗
PubMed2005

Afuni, a novel transforming growth factor-beta gene is involved in arm regeneration by the brittle star Amphiura filiformis.

The bone morphogenetic proteins (BMPs) are a family of the transforming growth factor-beta (TGF-beta) superfamily that perform multiple roles during vertebrate and invertebrate development. Here, we report the molecular cloning of a novel BMP from regenerating arms of the ophiuroid Amphiura filiformis. The theoretically translated amino acid sequence of this novel BMP has high similarity to that of the sea urchin BMP univin. This novel BMP has been named afuni. Whole-mount in situ hybridisation implicates afuni in arm regeneration. Expression occurs in distinct proximal and distal regions of late regenerates (3- and 5-week postablation). These sites are at different stages of regeneration, suggesting multiple roles for this gene in adult arm development. Cellular expression of this gene occurs in migratory cells within the radial water canal (RWC) of regenerating and nonregenerating arms. These migrating coelomocytes suggest a key role for the coelomic RWC as a source of the cellular material for use in arm regeneration by A. filiformis.

Amino Acid Sequence↗
PubMed2001

A population of caudally migrating cranial neural crest cells: functional and evolutionary implications.

The deployment of the cranial neural crest is central to the patterning of the skeletomuscular elements of the vertebrate head, with cranial muscles invariably attaching to skeletal elements formed by crest from the same axial level. Here we demonstrate, through gene expression analysis, ablation studies and fate-mapping, the existence of a population of caudally migrating cranial crest that arise from the postotic neural tube. As with the rest of the postotic crest, these cells express the transcription factor Mafb, and this marker can be used to highlight their posterior migration. They pass out between the anterior somite and the otic vesicle, before turning caudally and running along the base of the somites. With long-term fate mapping, we show that these cells migrate to the clavicle and settle at the site of formation of the attachment point for the cleidohyoid muscle. As such, the influence of the cranial neural crest in organising skeletomuscular connectivity seems to extend beyond the head into the trunk. These results are of further importance as they help explain how, even though the pectoral girdle and the skull became physically dissociated during tetrapod evolution, skeletomuscular connectivity has been maintained.

Animals↗
PubMed2001

Connexin43 gap junction protein plays an essential role in morphogenesis of the embryonic chick face.

Normal outgrowth and fusion of facial primordia during vertebrate development require interaction of diverse tissues and co-ordination of many different signalling pathways. Gap junction channels, made up of subunits consisting of connexin proteins, facilitate communication between cells and are implicated in embryonic development. Here we describe the distribution of connexin43 and connexin32 gap junction proteins in the developing chick face. To test the function of connexin43 protein, we applied antisense oligodeoxynucleotides that specifically reduced levels of connexin43 protein in cells of early chick facial primordia. This resulted in stunting of primordia outgrowth and led to facial defects. Furthermore, cell proliferation in regions of facial primordia that normally express high levels of connexin43 protein was reduced and this was associated with lower levels of Msx-1 expression. Facial defects arise when retinoic acid is applied to the face of chick embryos at later stages. This treatment also resulted in significant reduction in connexin43 protein, while connexin32 protein expression was unaffected. Taken together, these results indicate that connexin43 plays an essential role during early morphogenesis and subsequent outgrowth of the developing chick face.

Animals↗
PubMed1998

Fate map of the developing chick face: analysis of expansion of facial primordia and establishment of the primary palate.

Developing facial primordia change shape substantially in stages leading up to primary palate formation. We investigated expansion of cell populations within each of the four facial primordia of chick embryos between HH-stages 20 and 28, by using DiI labelling. Populations of cells centred around the nasal pits in the upper face, the midline of the paired mandibular primordia in the lower face, and at sites of fusion contribute most to overall expansion. Abundant Msx-1 transcripts are found in regions of high expansion, and Fgf-8 transcripts are seen in ectoderm associated with some of these regions. Many cell populations display preferential expansion along one axis. Maxillary and mandibular primordia cell populations expand along the proximodistal axis, whereas at the distal tip of the frontonasal mass, cell populations expand mediolaterally. Thus outgrowth occurs at the tips of mandibular and maxillary primordia, but at the base of the frontonasal mass. At regions where adjacent primordia abut each other, we found bidirectional movement of cells between primordia, unidirectional movement or could detect no movement at all. Regions of highest expansion in each primordium have the highest percentage of S phase labelled cells. Cell death occurs in some regions of low expansion but it seems likely that cell rearrangements and intercalations also contribute to shaping. These rearrangements could be associated with stretching of the primordia by neighbouring tissues. Treatment of chick embryos with retinoic acid causes clefts of the primary palate (Tamarin et al. [1984] J. Embryol. Exp. Morphol. 84:105-123). We found a decrease in expansion of cell populations that normally contribute to primary palate formation but surprisingly little ectopic cell death. Expansion of other cell populations in the treated upper face was more even rather than directed. This further supports the idea that tension exerted by neighbouring tissues plays a major role in global shaping of the upper face.

Animals↗
PubMedDate not supplied

The evolution of the pectoral girdle.

The pectoral girdle articulates the forelimb with the axial skeleton in all vertebrates with paired anterior appendages. The structure of the pectoral girdle and its position along the axial skeleton has changed significantly during vertebrate evolution. These morphological changes have been well described, but there is little comparative embryology to indicate how these changes may have occurred. It is equally obscure how the muscles that connect the head with the pectoral girdle have maintained appropriate attachments even though these 2 structures have become separated. Here I review the changes in the pectoral girdle across different vertebrate taxa, indicating, where known, the developmental mechanisms underlying these changes. I also suggest how the muscular connections between the head and pectoral girdle have been maintained between these once adjacent bones, displaced during vertebrate evolution.

Animals↗