Distinct effects of caudalizing factors on regional specification of embryonic stem cell-derived neural precursors.

摘要: Abstract Recent embryological studies have implicated several “caudalizing factors” in the caudal specification of central nervous system (CNS). In this study, we examined effects three candidate caudalizing factors on neural precursors induced from embryonic stem (ES) cells by stromal cell-derived inducing activity (SDIA) method. Among retinoic acid (RA), Wnt and FGF signals, RA causes strongest level caudalization: suppression forebrain differentiation promotion CNS specification. Obvious telencephalic marker Bf1 that Otx2 occur at 2×10−8 2×10−7 M, respectively. Activation genes such as Hoxb9 is observed a dose-dependent manner over range 2×10−9–2×10−6 M. Suppression has narrow critical period response during early culture phase. contrast, significant induction evoked 1-day exposure to any time between days 3 8. treatment not only induces but also inhibits ventral tissues, particularly floor plate cells. FGF4 partial caudalization while Wnt-3A exhibits weak activities presence RA. These findings provide useful information proper selection combination signaling molecules, doses timing for steering ES cell into fates.