The novel gene asb11: a regulator of the size of the neural progenitor compartment.
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.
Diks
Sander H
SH
Department of Cell Biology, University Medical Center Groningen, University of Groningen, NL-9713 AV Groningen, Netherlands.
Bink
Robert J
RJ
van de Water
Sandra
S
Joore
Jos
J
van Rooijen
Carina
C
Verbeek
Fons J
FJ
den Hertog
Jeroen
J
Peppelenbosch
Maikel P
MP
Zivkovic
Danica
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D049109:Cell Proliferation; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D024002:HMGB Proteins / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D055748:SOXB1 Transcription Factors; D013234:Stem Cells / Q000378:metabolism*; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D024002:HMGB Proteins; D006609:High Mobility Group Proteins; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C514282:Asb11 protein, zebrafish; C527782:SOX2 protein, human; C527785:SOX3 protein, human; C527784:Sox2 protein, rat; C486337:neurog1 protein, zebrafish