Specific regulation of cyclins D1 and D2 by FGF and Shh signaling coordinates cell cycle progression, patterning, and differentiation during early steps of spinal cord development.
In the vertebrate embryo, spinal cord elongation requires FGF signaling that promotes the continuous development of the posterior nervous system by maintaining a stem zone of proliferating neural progenitors. Those escaping the caudal neural stem zone, which is expressed to Shh signal, initiate ventral patterning in the neural groove before starting neuronal differentiation in the neural tube. Here we investigated the integration of D-type cyclins, known to govern cell cycle progression under the control of extracellular signals, in the program of spinal cord maturation. In chicken embryo, we find that cyclin D2 is preferentially expressed in the posterior neural plate, whereas cyclin D1 appears in the neural groove. We demonstrated by loss- and gain-of-function experiments that FGF signaling maintains cyclin D2 in the immature caudal neural epithelium, while Shh activates cyclin D1 in the neural groove. Moreover, forced maintenance of cyclin D1 or D2 in the neural tube favors proliferation at the expense of neuronal differentiation. These results contribute to our understanding of how the cell cycle control can be linked to the patterning programs to influence the balance between proliferation and neuronal differentiation in discrete progenitors domains.
Centre de Biologie du Développement, CNRS UMR5547 Bât 4R3, 31062 Toulouse cedex, France.
Valérie
V
Lobjois
Bertrand
B
Benazeraf
Nicolas
N
Bertrand
François
F
Medevielle
Fabienne
F
Pituello
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning; D002453:Cell Cycle; D002454:Cell Differentiation; D002642:Chick Embryo; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D008959:Models, Neurological; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D016213:Cyclins; D017931:DNA Primers; D053823:Hedgehog Proteins; D015534:Trans-Activators; D019938:Cyclin D1; D005346:Fibroblast Growth Factors