PubMed · 3674121
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G A Machin, G H Sperber. 1987. Lessons from conjoined twins.. https://doi.org/10.1002/ajmg.1320280113
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Several members of the kallikrein-related peptidase family of serine proteases have proteolytic activities that may affect cancer progression; however, the in vivo significance of these activities remains uncertain. We have demonstrated that expression of PSA or KLK4, but not KLK2, in PC-3 prostate cancer cells changed the cellular morphology from epithelial to spindle-shaped, markedly reduced E-cadherin expression, increased vimentin expression and increased cellular migration. These changes are indicative of an epithelial to mesenchymal transition (EMT), a process important in embryonic development and cancer progression. The potential novel role of kallikrein-related peptidases in this process is the focus of this brief review.
The serotonergic (5HT) system plays a key role in modulating behaviors, such as appetite and anxiety and has been implicated in many human disorders of mood and mind. Recent studies have begun to identify the signaling molecules and transcriptional cascades governing 5HT neuron development in the hindbrain. Already at early stages, local differences in requirements of 5HT neuron development have become apparent. These studies point toward cryptic heterogeneity amongst 5HT neurons and suggest that 5HT neuron determination and differentiation may be more flexible and less absolute biologic processes than might have been expected. Ultimately, the intrinsic heterogeneity and environmental sensitivity of 5HT neurons may help explain the variability observed in some human behavioral disorders, such as autism spectrum disorder, and the less predictable behavioral consequences of fetal alcohol syndrome.
Sonic hedgehog, SHH, is required for patterning the limb. The array of skeletal elements that compose the hands and feet, and the ordered arrangement of these bones to form the pattern of fingers and toes are dependent on SHH. The mechanism of action of SHH in the limb is not fully understood; however, an aspect that appears to be important is the localized, asymmetric expression of Shh. Shh is expressed in the posterior margin of the limb bud in a region defined as the zone of polarizing activity (ZPA). Analysis of mouse mutants which have polydactyly (extra toes) shows that asymmetric expression of Shh is lost due to the appearance of an ectopic domain of expression in the anterior limb margin. One such polydactylous mouse mutant, sasquatch (Ssq), maps to the corresponding chromosomal region of the human condition pre-axial polydactyly (PPD) and thus represents a model for this condition. The mutation responsible for Ssq is located 1 Mb away from the Shh gene; however, the mutation disrupts a long-range cis-acting regulator of Shh expression. By inference, human pre-axial polydactyly results from a similar disruption of Shh expression. Other human congenital abnormalities also map near the pre-axial polydactyly locus, suggesting a major chromosomal region for limb dysmorphologies. The distinct phenotypes range from loss of all bones of the hands and feet to syndactyly of the soft tissue and fusion of the digits. We discuss the role played by Shh expression in mouse mutant phenotypes and the human limb dysmorphologies.