Biomedical subjects

Jill A Helms

Publications and source records attributed to Jill A Helms.

22 records · Page 2Linked to original sources

PubMed2003

A zone of frontonasal ectoderm regulates patterning and growth in the face.

A fundamental set of patterning genes may define the global organization of the craniofacial region. One of our goals has been to identify these basic patterning genes and understand how they regulate outgrowth of the frontonasal process, which gives rise to the mid and upper face. We identified a molecular boundary in the frontonasal process ectoderm, defined by the juxtaposed domains of Fibroblast growth factor 8 and Sonic hedgehog, which presaged the initial site of frontonasal process outgrowth. Fate maps confirmed that this boundary region later demarcated the dorsoventral axis of the upper beak. Ectopic transplantation of the ectodermal boundary region activated a cascade of molecular events that reprogrammed the developmental fate of neural crest-derived mesenchyme, which resulted in duplications of upper and lower beak structures. We discuss these data in the context of boundary/morphogen models of patterning, and in view of the recent controversy regarding neural crest pre-patterning versus neural crest plasticity.

Animals↗

PubMed2003

Altered fracture repair in the absence of MMP9.

The regeneration of adult skeletal tissues requires the timely recruitment of skeletal progenitor cells to an injury site, the differentiation of these cells into bone or cartilage, and the re-establishment of a vascular network to maintain cell viability. Disturbances in any of these cellular events can have a detrimental effect on the process of skeletal repair. Although fracture repair has been compared with fetal skeletal development, the extent to which the reparative process actually recapitulates the fetal program remains uncertain. Here, we provide the first genetic evidence that matrix metalloproteinase 9 (MMP9) regulates crucial events during adult fracture repair. We demonstrate that MMP9 mediates vascular invasion of the hypertrophic cartilage callus, and that Mmp9(-/-) mice have non-unions and delayed unions of their fractures caused by persistent cartilage at the injury site. This MMP9- dependent delay in skeletal healing is not due to a lack of vascular endothelial growth factor (VEGF) or VEGF receptor expression, but may instead be due to the lack of VEGF bioavailability in the mutant because recombinant VEGF can rescue Mmp9(-/-) non-unions. We also found that Mmp9(-/-) mice generate a large cartilage callus even when fractured bones are stabilized, which implicates MMP9 in the regulation of chondrogenic and osteogenic cell differentiation during early stages of repair. In conclusion, the resemblance between Mmp9(-/-) fetal skeletal defects and those that emerge during Mmp9(-/-) adult repair offer the strongest evidence to date that similar mechanisms are employed to achieve bone formation, regardless of age.

Animals↗

PubMed2002

A model for intramembranous ossification during fracture healing.

We have developed a method to study the molecular basis of intramembranous fracture healing. Unlike intramedullary rods that permit rotation of the fractured bone segments, our murine model relies on an external fixation device to provide stabilization. In this study we compare stabilized fracture callus tissues with callus tissues from non-stabilized fractures during the inflammatory, soft callus, hard callus, and remodeling stages of healing. Histological analyses indicate that stabilized fractures heal with virtually no evidence of cartilage whereas non-stabilized fractures produce abundant cartilage at the fracture site. Expression patterns of collagen type IIa (colIIa) and osteocalcin (oc) reveal that mesenchymal cells at the fracture site commit to either a chondrogenic or an osteogenic lineage during the earliest stages of healing. The mechanical environment influences this cell fate decision, since mesenchymal cells in a stabilized fracture express oc and fail to express colIIa. Future studies will use this murine model of intramembranous fracture healing to explore, at a molecular level, how the mechanical environment exerts its influence on healing of a fracture.

Animals↗

PubMed2002

Prenatal morphogenesis of the human mental foramen.

The mental foramen, at first glance, merely looks like a hole where the mental nerve and the vascular bundle runs through. From a morphogenetic point of view, however, the mental foramen is a suitable model to study the development of a structure where different components are involved. To understand this developmental process, a three-dimensional description at different developmental stages first has to be given. From histological serial sections of human embryos and fetuses, ranging in size from 19 to 117 mm crown rump length (CRL), three-dimensional reconstructions of the foraminar regions were made. Outline and form of the developing foramen, size, course of the mental nerve and the adjacent blood vessels could be shown in detail. In this way, the formation of these structures became concrete in three dimensions. In the future, to understand the mechanisms regulating this complex system, where a nerve and blood vessels became successively surrounded by bone, molecular biological data have to be correlated with morphological findings.

Chin↗