Cyclin A is a pivotal regulatory protein which, in mammalian cells, is involved in the S phase of the cell cycle. Transcription of the human cyclin A gene is cell cycle regulated. We have investigated the role of the cyclic AMP (cAMP)-dependent signalling pathway in this cell cycle-dependent control. In human diploid fibroblasts (Hs 27), induction of cyclin A gene expression at G 1 /S is stimulated by 8-bromo-cAMP and suppressed by the protein kinase A inhibitor H89, which was found to delay S phase entry. Transfection experiments showed that the cyclin A promoter is inducible by activation of the adenylyl cyclase signalling pathway. Stimulation is mediated predominantly via a cAMP response element (CRE) located at positions ؊80 to ؊73 with respect to the transcription initiation site and is able to bind CRE-binding proteins and CRE modulators. Moreover, activation by phosphorylation of the activators CRE-binding proteins and CRE modulator and levels of the inducible cAMP early repressor are cell cycle regulated, which is consistent with the pattern of cyclin A inducibility by cAMP during the cell cycle. These results suggest that the CRE is, at least partly, implicated in stimulation of cyclin A transcription at G 1 /S.Cyclins are a group of proteins which are periodically synthesized and degraded during the cell cycle. This enables them to activate at appropriate times the cyclin-dependent kinases (cdks), whose activity is needed to drive the cells through the cell cycle (for recent reviews, see references 5, 37, and 41).In higher eukaryotes, cyclin proteins have been classified as A-, B-, C-, D-, E-, or G-type according to sequence comparison. A-and B-type cyclins associate with cdc2 (cdk1), whose activity is required for entry into mitosis (47). Additional cyclins, which function earlier in the cell cycle, have been identified more recently. D-type cyclins are involved in G 1 progression (33) in association with cdk4 and cdk6. Cyclin E has been implicated in the initiation of DNA replication and is associated with cdk2 at the G 1 /S transition (12, 28).

SummaryWhile neurogenic stem cells have been identified in rodent and human skin, their manipulation and further characterization are hampered by a lack of specific markers. Here, we perform genetic tracing of the progeny of boundary cap (BC) cells, a neural-crest-derived cell population localized at peripheral nerve entry/exit points. We show that BC derivatives migrate along peripheral nerves to reach the skin, where they give rise to terminal glia associated with dermal nerve endings. Dermal BC derivatives also include cells that self-renew in sphere culture and have broad in vitro differentiation potential. Upon transplantation into adult mouse dorsal root ganglia, skin BC derivatives efficiently differentiate into various types of mature sensory neurons. Together, this work establishes the embryonic origin, pathway of migration, and in vivo neurogenic potential of a major component of skin stem-like cells. It provides genetic tools to study and manipulate this population of high interest for medical applications.