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Biomedical subjects

S Ruffins

Publications and source records attributed to S Ruffins.

5 recordsLinked to original sources

A critical period for conversion of ectodermal cells to a neural crest fate.

Previously, we found that interactions between neural and nonneural ectoderm can generate neural crest cells, with both the ectodermal and the neuroepithelial cells contributing to induced population (M. A. J. Selleck and M. Bronner-Fraser, 1995, Development 121, 525-538). To further characterize the ability of ectodermal cells to form neural crest, we have challenged their normal fate by transplanting them into the neural tube. To ensure that the ectoderm was from nonneural regions, we utilized extraembryonic ectoderm (the proamnion) and transplanted it into the presumptive midbrain of 1. 5-day-old chick embryos. We observed that the grafted ectoderm has the capacity to adopt a neural crest fate, responding within a few hours of surgery by turning on neural crest markers HNK-1 and Slug. However, the competence of the ectoderm to respond to neural crest-inducing signals is time limited, declining rapidly in donors older than the 10-somite stage. Similarly, the inductive capacity of the host midbrain declines in a time-dependent fashion. Our results show that extraembryonic ectoderm has the capacity to form neural crest cells given proper inducing signals, expressing both morphological and molecular markers characteristic of neural crest cells.

Animals↗

Early migrating neural crest cells can form ventral neural tube derivatives when challenged by transplantation.

Once neural crest cells undergo an epithelial-mesenchymal transition to leave the neural tube, it has been classically assumed that they are fated to differentiate within the neural crest lineage. To test this idea, we challenged the developmental potential of recently emigrated neural crest cells by transplanting them into the ventral portion of the neural tube at the open neural plate stage. Newly migrating neural crest cells were isolated in tissue culture, labeled with the lipophilic dye DiI, and microinjected into the ventral portion of the neural plate. After 2 days, some neural crest cells became incorporated into the neuroepithelium in positions characteristic of floor plate cells and motor neurons. Some of the labeled cells within the ventral neural tube expressed FP-1, characteristic of floor plate cells. A few labeled cells were found in positions characteristic of motor neurons and expressed islet-1. In contrast, neural crest cells transplanted onto neural crest pathways expressed the HNK-1 epitope, but no ventral neural tube markers. Injection of neural crest cells into the mesenchyme adjacent to the notochord or culturing them in the presence of Sonic hedgehog failed to elicit FP-1 expression. These results suggest that migrating neural crest cells are flexible in their fate and retain the ability to form neural tube derivatives even after emigrating from the neural tube.

Animals↗

Dorsal hindbrain ablation results in rerouting of neural crest migration and changes in gene expression, but normal hyoid development.

Our previous studies have shown that hindbrain neural tube cells can regulate to form neural crest cells for a limited time after neural fold removal (Scherson, T., Serbedzija, G., Fraser, S. E. and Bronner-Fraser, M. (1993). Development 188, 1049-1061; Sechrist, J., Nieto, M. A., Zamanian, R. T. and Bronner-Fraser, M. (1995). Development 121, 4103-4115). In the present study, we ablated the dorsal hindbrain at later stages to examine possible alterations in migratory behavior and/or gene expression in neural crest populations rostral and caudal to the operated region. The results were compared with those obtained by misdirecting neural crest cells via rhombomere rotation. Following surgical ablation of dorsal r5 and r6 prior to the 10 somite stage, r4 neural crest cells migrate along normal pathways toward the second branchial arch. Similarly, r7 neural crest cells migrate primarily to the fourth branchial arch. When analogous ablations are performed at the 10-12 somite stage, however, a marked increase in the numbers of DiI/Hoxa-3-positive cells from r7 are observed within the third branchial arch. In addition, some DiI-labeled r4 cells migrate into the depleted hindbrain region and the third branchial arch. During their migration, a subset of these r4 cells up-regulate Hoxa-3, a transcript they do not normally express. Krox20 transcript levels were augmented after ablation in a population of neural crest cells migrating from r4, caudal r3 and rostral r3. Long-term survivors of bilateral ablations possess normal neural crest-derived cartilage of the hyoid complex, suggesting that misrouted r4 and r7 cells contribute to cranial derivatives appropriate for their new location. In contrast, misdirecting of the neural crest by rostrocaudal rotation of r4 through r6 results in a reduction of Hoxa-3 expression in the third branchial arch and corresponding deficits in third arch-derived structures of the hyoid apparatus. These results demonstrate that neural crest/tube progenitors in the hindbrain can compensate by altering migratory trajectories and patterns of gene expression when the adjacent neural crest is removed, but fail to compensate appropriately when the existing neural crest is misrouted by neural tube rotation.

Age Factors↗

Physical and sexual abuse in adolescent girls with borderline personality disorder.

Recent investigations suggest that a history of childhood sexual abuse may be associated with borderline personality disorder. This study compares a group of female adolescents diagnosed as borderline with a control group for history of physical and sexual abuse. History of both forms of abuse, particularly sexual, distinguishes the two groups. Results point to the impact of repeated trauma on character structure, cognitive functioning, and Axis II symptomatology.

Adolescent↗

Object relations in borderline adolescents.

Although pathological object relations is a core aspect of borderline psychopathology, few studies have examined borderline object relations empirically, and none has focused on borderline adolescents. The present study examined four dimensions of object relations, as measured by the Thematic Apperception Test, in a sample of adolescent borderlines, psychiatric comparison subjects, and normals. These dimensions are complexity of object representations, affect-tone of relationship paradigms, capacity for emotional investment in relationships and moral standards, and understanding of social causality. Borderlines differed significantly from both comparison groups in several distinct ways, supporting some aspects of psychoanalytic theories of borderline object relations, while challenging others. Borderline adolescents have a malevolent object world, a relative incapacity to invest in others in a non-need-gratifying way, and a tendency to attribute motivation to others in simple, illogical, and idiosyncratic ways. Their object representations, however, can be quite complex, suggesting something other than a preoedipal arrest.

Adolescent↗