On a dynamic reaction-diffusion mechanism: The spatial patterning of teeth primordia in the alligator

It is now well established both theoretically and, more recently, experimentally, that steady-state spatial chemical concentration patterns can be formed by a number of specific reaction–diffusion systems. Reaction–diffusion models have been widely applied to biological pattern formation problems. Here we propose a model mechanism for the initiation and spatial positioning of teeth primordia in the alligator, Alligator mississippiensis, which, from a reaction–diffusion theory, introduces, among other things, a new element, namely the effect of domain growth on dynamic spatial pattern formation. Detailed embryological studies by Westergaard and Ferguson (B. Westergaard and M. W. J. Ferguson, J. Zool. Lond., 1986, 210, 575; 1987, 212, 191; Am. J. Anatomy, 1990, 187, 393) show that jaw growth plays a crucial role in the developmental patterning of the tooth initiation process. Based on biological data we develop a reaction–diffusion mechanism, which crucially includes domain growth. The model can reproduce the spatial pattern development of the first seven teeth primordia in the lower half jaw of A. mississippiensis. The results for the precise spatio temporal sequence compare well with detailed developmental experiments

In ovo time-lapse analysis of chick hindbrain neural crest cell migration shows cell interactions during migration to the branchial arches

Hindbrain neural crest cells were labeled with DiI and followed in ovo using a new approach for long-term time-lapse confocal microscopy. In ovo imaging allowed us to visualize neural crest cell migration 2-3 times longer than in whole embryo explant cultures, providing a more complete picture of the dynamics of cell migration from emergence at the dorsal midline to entry into the branchial arches. There were aspects of the in ovo neural crest cell migration patterning which were new and different. Surprisingly, there was contact between neural crest cell migration streams bound for different branchial arches. This cell-cell contact occurred in the region lateral to the otic vesicle, where neural crest cells within the distinct streams diverted from their migration pathways into the branchial arches and instead migrated around the otic vesicle to establish a contact between streams. Some individual neural crest cells did appear to cross between the streams, but there was no widespread mixing. Analysis of individual cell trajectories showed that neural crest cells emerge from all rhombomeres (r) and sort into distinct exiting streams adjacent to the even-numbered rhombomeres. Neural crest cell migration behaviors resembled the wide diversity seen in whole embryo chick explants, including chain-like cell arrangements; however, average in ovo cell speeds are as much as 70% faster. To test to what extent neural crest cells from adjoining rhombomeres mix along migration routes and within the branchial arches, separate groups of premigratory neural crest cells were labeled with DiI or DiD. Results showed that r6 and r7 neural crest cells migrated to the same spatial location within the fourth branchial arch. The diversity of migration behaviors suggests that no single mechanism guides in ovo hindbrain neural crest cell migration into the branchial arches. The cell-cell contact between migration streams and the co-localization of neural crest cells from adjoining rhombomeres within a single branchial arch support the notion that the pattern of hindbrain neural crest cell migration emerges dynamically with cell-cell communication playing an important guidance role

In ovo time-lapse analysis after dorsal neural tube ablation shows rerouting of chick hindbrain neural crest

Previous analyses of single neural crest cell trajectories have suggested important roles for interactions between neural crest cells and the environment, and amongst neural crest cells. To test the relative contribution of intrinsic versus extrinsic information in guiding cells to their appropriate sites, we ablated subpopulations of premigratory chick hindbrain neural crest and followed the remaining neural crest cells over time using a new in ovo imaging technique. Neural crest cell migratory behaviors are dramatically different in ablated compared with unoperated embryos. Deviations from normal migration appear either shortly after cells emerge from the neural tube or en route to the branchial arches, areas where cell-cell interactions typically occur between neural crest cells in normal embryos. Unlike the persistent, directed trajectories in normal embryos, neural crest cells frequently change direction and move somewhat chaotically after ablation. In addition, the migration of neural crest cells in collective chains, commonly observed in normal embryos, was severely disrupted. Hindbrain neural crest cells have the capacity to reroute their migratory pathways and thus compensate for missing neural crest cells after ablation of neighboring populations. Because the alterations in neural crest cell migration are most dramatic in regions that would normally foster cell-cell interactions, the trajectories reported here argue that cell-cell interactions have a key role in the shaping of the neural crest migration

Multiscale mechanisms of cell migration during development: theory and experiment

Long-distance cell migration is an important feature of embryonic development, adult morphogenesis and cancer, yet the mechanisms that drive subpopulations of cells to distinct targets are poorly understood. Here, we use the embryonic neural crest (NC) in tandem with theoretical studies to evaluate model mechanisms of long-distance cell migration. We find that a simple chemotaxis model is insufficient to explain our experimental data. Instead, model simulations predict that NC cell migration requires leading cells to respond to long-range guidance signals and trailing cells to short-range cues in order to maintain a directed, multicellular stream. Experiments confirm differences in leading versus trailing NC cell subpopulations, manifested in unique cell orientation and gene expression patterns that respond to non-linear tissue growth of the migratory domain. Ablation experiments that delete the trailing NC cell subpopulation reveal that leading NC cells distribute all along the migratory pathway and develop a leading/trailing cellular orientation and gene expression profile that is predicted by model simulations. Transplantation experiments and model predictions that move trailing NC cells to the migratory front, or vice versa, reveal that cells adopt a gene expression profile and cell behaviors corresponding to the new position within the migratory stream. These results offer a mechanistic model in which leading cells create and respond to a cell-induced chemotactic gradient and transmit guidance information to trailing cells that use short-range signals to move in a directional manner

Distinct modes of floor plate induction in the chick embryo

To begin to reconcile models of floor plate formation in the vertebrate neural tube, we have performed experiments aimed at understanding the development of the early floor plate in the chick embryo. Using real-time analyses of cell behaviour, we provide evidence that the principal contributor to the early neural midline, the future anterior floor plate, exists as a separate population of floor plate precursor cells in the epiblast of the gastrula stage embryo, and does not share a lineage with axial mesoderm. Analysis of the tissue interactions associated with differentiation of these cells to a floor plate fate reveals a role for the nascent prechordal mesoderm, indicating that more than one inductive event is associated with floor plate formation along the length of the neuraxis. We show that Nr1, a chick nodal homologue, is expressed in the nascent prechordal mesoderm and we provide evidence that Nodal signalling can cooperate with Shh to induce the epiblast precursors to a floor-plate fate. These results indicate that a shared lineage with axial mesoderm cells is not a pre-requisite for floor plate differentiation and suggest parallels between the development of the floor plate in amniote and anamniote embryos

Conscientious refusal or conscientious provision: we can't have both

Some authors argue that it is permissible for clinicians to conscientiously provide abortion services because clinicians are already allowed to conscientiously refuse to provide certain services. Call this the symmetry thesis. We argue that on either of the two main understandings of the aim of the medical profession—what we will call “pathocentric” and “interest-centric” views—conscientious refusal and conscientious provision are mutually exclusive. On pathocentric views, refusing to provide a service that takes away from a patient's health is professionally justified because there are compelling reasons, based on professional standards, to refuse to provide that service (e.g., it does not heal, and it is contrary to the goals of medicine). However, providing that same service is not professionally justified when providing that service would be contrary to the goals of medicine. Likewise, the thesis turns out false on interest-centric views. Refusing to provide a service is not professionally justified when that service helps the patient fulfill her autonomous preferences because there are compelling reasons, based on professional standards, to provide that service (e.g., it helps her achieve her autonomous preferences, and it would be contrary to the goals of medicine to deny her that service). However, refusing to provide that same service is not professionally justified when refusing to provide that service would be contrary to the goals of medicine. As a result, on either of the two most plausible views on the goals of medicine, the symmetry thesis turns out false