N-cadherin protein distribution in normal embryos and in embryos carrying mutations in the homeobox gene Hoxa-4.

N-cadherin is a calcium-dependent adhesion molecule with a potential role in a variety of morphogenetic events. Although a dynamic pattern of expression in the mouse embryo has been suggested by in situ hybridization analysis, to date there has been no report of N-cadherin protein expression. In this immunohistochemical study we surveyed N-cadherin protein expression in the mid-late gestation mouse embryo utilizing a recently characterized monoclonal antibody. We found N-cadherin expression in a wide array of tissues, including the brain, the eye, various cranial ganglia, the spinal cord, spinal ganglia, somites, vertebral and limb cartilage and perichondria, the developing lung and kidney, the enteric nervous system, and germ cells. These results suggest that N-cadherin protein expression, as in the chick embryo, correlates with the segregation of cells and with organogenesis. As cadherins have been proposed as targets of vertebrate Hox genes, we also examined N-cadherin expression in two lines of Hoxa-4 mutant mice. We did not observe any alterations in N-cadherin expression in either Hoxa-4 null embryos or in transgenic embryos that overexpress Hoxa-4 in the mesenchyme of the gut. However, the partial overlap in expression between Hox genes and N-cadherin, and the likelihood of redundancy in the regulation of target genes, leaves open the possibility that cadherins are direct or indirect targets of Hox genes during mouse embryogenesis.

Dural infiltration of metastatic Hodgkin's lymphoma.

Hodgkin's disease is a neoplasm of clonal Reed-Sternberg cells. Intracranial Hodgkin's lymphoma is rare. We present a unique case of a 57-year-old woman with secondary intracranial lymphoma infiltrating the dura. Her past medical history included Hodgkin's lymphoma from which she was deemed to be in remission at the time of presentation. Following an acute onset of seizures, she underwent radiological investigations that demonstrated an enhancing right-sided temporal dural-based space occupying lesion. Histopathological findings revealed nodular sclerosing Hodgkin's lymphoma with pathognomonic Reed-Sternberg cells. In cases of intracranial lesions with dural infiltration, Hodgkin's lymphoma should be considered in the diagnosis.

Expression of the murine Hoxa4 gene requires both autoregulation and a conserved retinoic acid response element.

Analysis of the regulatory regions of the Hox genes has revealed a complex array of positive and negative cis-acting elements that control the spatial and temporal pattern of expression of these genes during embryogenesis. In this study we show that normal expression of the murine Hoxa4 gene during development requires both autoregulatory and retinoic acid-dependent modes of regulation. When introduced into a Hoxa4 null background, expression of a lacZ reporter gene driven by the Hoxa4 regulatory region (Hoxa4/lacZ) is either abolished or significantly reduced in all tissues at E10. 5-E12.5. Thus, the observed autoregulation of the Drosophila Deformed gene is conserved in a mouse homolog in vivo, and is reflected in a widespread requirement for positive feedback to maintain Hoxa4 expression. We also identify three potential retinoic acid response elements in the Hoxa4 5' flanking region, one of which is identical to a well-characterized element flanking the Hoxd4 gene. Administration of retinoic acid to Hoxa4/lacZ transgenic embryos resulted in stage-dependent ectopic expression of the reporter gene in the neural tube and hindbrain. When administered to Hoxa4 null embryos, however, persistent ectopic expression was not observed, suggesting that autoregulation is required for maintenance of the retinoic acid-induced expression. Finally, mutation of the consensus retinoic acid response element eliminated the response of the reporter gene to exogenous retinoic acid, and abolished all embryonic expression in untreated embryos, with the exception of the neural tube and prevertebrae. These data add to the evidence that Hox gene expression is regulated, in part, by endogenous retinoids and autoregulatory loops.