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The molecular organization of the zebrafish brain and its relation to neuroanatomical divisions are still largely unknown. In this study we have analyzed the expression of a small transcript encoding for the IQ containing polypeptide Pcp4a in developing and juvenile zebrafish. The transcript is exclusively expressed in neural structures with a pattern that is highly specific for restricted domains and cell populations throughout development, and it allows us to follow the development of these structures at different times. The expression of pcp4a characterizes the dorsocaudal telencephalon, dorsal habenula, pretectal nuclei, preglomerular complex, mammillary bodies, and deep layers of the optic tectum and is a hallmark of a subpopulation of reticulospinal neurons. In the telencephalon, comparison of the expression of pcp4a with other pallial markers showed a rostrocaudal gradient in the expression of these genes, which suggests that the dorsal telencephalon of zebrafish may be organized in distinct areas with different molecular natures. Pcp4 has been involved in modulating calcium signals and in binding to calmodulin, but its precise role in neuronal functions is not known. The analysis of pcp4a expression and localization in the zebrafish brain suggests that pcp4a may be a useful marker for sensory and some motor neuronal circuitries and for telencephalic areas processing sensory inputs.

Kinins are key pro-inflammatory peptides that exhibit mitogenic effects in tissue-specific cellular systems. Since the life span of the keratinocyte is regulated by receptors that control proliferation and differentiation, and since both processes are affected during wound healing, we have examined the consequence of kinin B2 receptors (B2R) activation in cultured human keratinocytes. Stimulation of keratinocytes by Lys-bradykinin (LBK) induced a rapid and sustained phosphorylation of 42/44 mitogen-activated protein kinase (MAPK) that translocated to the nucleus, and decreased only after 120 min of stimulation. Kinin B1 and B2 receptor (B1R and B2R) antagonists showed that phosphorylation was mainly because of B2R activation. The GF109203X inhibitor almost completely abolished the effect of LBK, suggesting the involvement of protein kinase C in the signal cascade. MAPK phosphorylation was partially dependent on epidermal growth factor receptor transactivation as assessed by the selective inhibitor, AG1478. LBK stimulation did not result in cell proliferation, but produced a rapid c-Fos expression, nuclear translocation of nuclear factor-kappaB, and a moderated (pro)filaggrin synthesis, indicating that it may modulate cell differentiation. Our results support the view that kinins may affect the life span of human keratinocytes and highlight the importance that kinin peptides may have in the pathogenesis and/or progression of skin diseases.

The isocortex is a distinctive feature of the mammalian brain, with no clear counterpart in other amniotes. There have been long controversies regarding possible homologues of this structure in reptiles and birds. The brains of the latter are characterized by the presence of a structure termed dorsal ventricular ridge (DVR), which receives ascending auditory and visual projections, and has been postulated to be homologous to parts of the mammalian isocortex (i.e., the auditory and the extrastriate visual cortices). Dissenting views, now supported by molecular evidence, claim that the DVR originates from a region termed ventral pallium, while the isocortex may arise mostly from the dorsal pallium (in mammals, the ventral pallium relates to the claustroamygdaloid complex). Although it is possible that in mammals the embryonic ventral pallium contributes cells to the developing isocortex, there is no evidence yet supporting this alternative. The possibility is raised that the expansion of the cerebral cortex in the origin of mammals was product of a generalized dorsalizing influence in pallial development, at the expense of growth in ventral pallial regions. Importantly, the evidence suggests that organization of sensory projections is significantly different between mammals and sauropsids. In reptiles and birds, some sensory pathways project to the ventral pallium and others project to the dorsal pallium, while in mammals sensory projections end mainly in the dorsal pallium. We suggest a scenario for the origin of the mammalian isocortex which relies on the development of associative circuits between the olfactory, the dorsal and the hippocampal cortices in the earliest mammals.