The Gja1 gene encoding the gap junction connexin 43 (Cx43) is dynamically regulated during limb morphogenesis. Transcript expression is found in many regions of the limb bud known to be important in regulating limb growth and patterning. In the newly emerged limb bud, Gja1 transcripts are first expressed in the ventrodistal margin of the ectoderm, and later transcript expression is localized to the apical ectodermal ridge (AER). Interestingly, transcript expression in the ventrodistal ectoderm is initiated left/right asymmetrically, with some strain backgrounds showing reverse sidedness in the fore vs. hindlimb buds. In legless, a mouse mutant exhibiting both limb and left/right patterning defects, Gja1 transcripts could not be detected in this region. However, in the iv/iv embryo, a mutant with randomization of body situs, the same pattern of Gja1 asymmetry was found in the limb ectoderm regardless of body situs. This suggests that Gja1 transcript expression is not directly linked to signaling pathways involved in specification of the left/right axis. In addition to transcript expression in the apical ectodermal ridge, Gja1 transcripts were also found at high levels in the ventral ectoderm. In the limb bud mesenchyme, Gja1 transcripts were distributed in a posterior‐distal gradient, coincident with tissue known to have polarizing activity. With limb outgrowth and the initiation of limb mesenchyme condensation, Gja1 transcripts were localized in the presumptive progress zone, and in the condensing mesenchyme. In more proximal regions of the limb where mesenchyme differentiation has been initiated, Gja1 transcripts were expressed only in the outer mesenchymal cells comprising the presumptive perichondrium. Further analysis of transgenic mice ectopically expressing Wnt‐1 in the limb mesenchyme revealed alterations in the pattern of Gja1 transcript expression in conjunction with the perturbation of limb mesenchyme condensation and differentiation. Together, these findings indicate that Cx43 gap junctions may mediate cell‐cell interactions important in cell signaling processes involved in limb growth and patterning. Dev. Genet. 21:290–300, 1997. © 1997 Wiley‐Liss, Inc.

The Gja1 gene encoding the gap junction connexin 43 (Cx43) is dynamically regulated during limb morphogenesis. Transcript expression is found in many regions of the limb bud known to be important in regulating limb growth and patterning. In the newly emerged limb bud, Gja1 transcripts are first expressed in the ventrodistal margin of the ectoderm, and later transcript expression is localized to the apical ectodermal ridge (AER). Interestingly, transcript expression in the ventrodistal ectoderm is initiated left/right asymmetrically, with some strain backgrounds showing reverse sidedness in the fore vs. hindlimb buds. In legless, a mouse mutant exhibiting both limb and left/right patterning defects, Gja1 transcripts could not be detected in this region. However, in the i.v./i.v. embryo, a mutant with randomization of body situs the same pattern of Gja1 asymmetry was found in the limb ectoderm regardless of body situs. This suggests that Gja1 transcript expression is not directly linked to signaling pathways involved in specification of the left/right axis. In addition to transcript expression in the apical ectodermal ridge, Gja1 transcripts were also found at high levels in the ventral ectoderm. In the limb bud mesenchyme, Gja1 transcripts were distributed in a posterior distal gradient, coincident with tissue known to have polarizing activity. With limb outgrowth and the initiation of limb mesenchyme condensation. Gja1 transcripts were localized in the presumptive progress zone, and in the condensing mesenchyme. In more proximal regions of the limb where mesenchyme differentiation has been initiated, Gja1 transcripts were expressed only in the outer mesenchymal cells comprising the presumptive perichondrium. Further analysis of transgenic mice ectopically expressing Wnt-1 in the limb mesenchyme revealed alterations in the pattern of Gja1 transcript expression in conjunction with the perturbation of limb mesenchyme condensation and differentiation. Together, these findings indicate that Cx43 gap junctions may mediate cell-cell interactions important in cell signaling processes involved in limb growth and patterning.

The annual number of cases of tuberculosis in New York City has increased since 1978. In addition, in 1991 a 1-month survey of cases of tuberculosis in New York City found that 33% of all cases were resistant to at least one drug. To determine susceptibility trends from 1987 to 1991, a period during which an unprecedented rise in resistant tuberculosis occurred in New York City, we reviewed the microbiology records of 44 New York City hospitals (comprising > 14,000 cases). The percentage of cases resistant to at least one drug rose from 19% in 1987 to 28% in 1991, and the percentage of cases resistant to isoniazid rose from 13% in 1987 to 23% in 1991, while resistance to at least both isoniazid and rifampin rose from 6% to 14%. The rise of multidrug-resistant tuberculosis occurred in all four surveyed boroughs (counties) of New York City. These data demonstrate how rapidly multidrug-resistant tuberculosis can appear, and they suggest that initial empirical regimens should be broadened at certain hospitals.