From a differential display designed to isolate genes that are down-regulated upon differentiation of the central nervous system in Danio rerio embryos, we isolated d-asb11 (ankyrin repeat and suppressor of cytokine signaling box–containing protein 11). Knockdown of the d-Asb11 protein altered the expression of neural precursor genes sox2 and sox3 and resulted in an initial relative increase in proneural cell numbers. This was reflected by neurogenin1 expansion followed by premature neuronal differentiation, as demonstrated by HuC labeling and resulting in reduced size of the definitive neuronal compartment. Forced misexpression of d-asb11 was capable of ectopically inducing sox2 while it diminished or entirely abolished neurogenesis. Overexpression of d-Asb11 in both a pluripotent and a neural-committed progenitor cell line resulted in the stimulus-induced inhibition of terminal neuronal differentiation and enhanced proliferation. We conclude that d-Asb11 is a novel regulator of the neuronal progenitor compartment size by maintaining the neural precursors in the proliferating undifferentiated state possibly through the control of SoxB1 transcription factors.
The novel gene asb11: a regulator of the size of the neural progenitor compartment
S.H. Diks and R.J. Bink contributed equally to this paper.
Abbreviations used in this paper: ASB, ankyrin repeat and SOCS box–containing protein; CNS, central nervous system; GAP-43, growth cone–associated protein 43; GCNF, germ cell nuclear factor; HMG, high mobility group; hpf, hours postfertilization; MO, morpholino; MT, myc tag; MTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; ngn1, neurogenin1; PCNA, proliferating cell nuclear antigen; PH3, phosphohistone-3; RA, retinoic acid; SOCS, suppressor of cytokine signaling.
Sander H. Diks, Robert J. Bink, Sandra van de Water, Jos Joore, Carina van Rooijen, Fons J. Verbeek, Jeroen den Hertog, Maikel P. Peppelenbosch, Danica Zivkovic; The novel gene asb11: a regulator of the size of the neural progenitor compartment . J Cell Biol 14 August 2006; 174 (4): 581–592. doi: https://doi.org/10.1083/jcb.200601081
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