Developmental changes in progenitor cell responsiveness to cytokines

Abstract

Multipotent progenitor cells have been identified within periventricular generative zones of the developing and adult brain. To determine whether the environmental responsiveness of these cells changes during development, progenitor cells were cultured from embryonic, postnatal, and adult rat brain in the presence of either basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF). Embryonic cells cultured as intact progenitor neurospheres proliferated more robustly in response to bFGF than to EGF, whereas proliferation of postnatal and adult progenitor cells was enhanced more by EGF than bFGF. Progenitor cells generated in the presence of either bFGF or EGF had the capacity to generate neurons, astrocytes, and oligodendrocytes at all developmental stages. Most embryonic and neonatal bFGF-generated cells differentiated predominantly into neurons, whereas late stage embryonic and neonatal EGF-generated progenitors largely remained in an undifferentiated state. However, later postnatal and adult progenitor species, irrespective of whether they were generated in the presence of bFGF or EGF, gave rise preferentially to astrocytes. Treatment with bone morphogenetic protein (BMP)2 or BMP7 enhanced astroglial differentiation and suppressed oligodendroglial differentiation of both EGF- and bFGF-generated progenitor species, suggesting that the effects of the BMPs are not dependent on EGF receptor activation. Thus, while central nervous system (CNS) progenitor cells retain multipotent capacity and responsiveness to the BMPs throughout development, they exhibit significant changes in other cellular response properties, perhaps reflecting differences in the requirements for specific generative versus regenerative events.

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

“…In early embryogenesis, inactivation of BMP signaling in the chick dorsal neural axis results in an increase in oligodendrogenesis (Mekki-Dauriac et al 2002). BMP-2 or BMP-4 treatment of cultured neural stem/progenitor cells inhibits oligodendrogenesis at all stages of development, whereas noggin treatment increases it (Mehler et al 1995;Gross et al 1996;Zhu et al 1999a). Diminished oligodendrocyte differentiation is also observed in transgenic mice overexpressing BMP-4, whereas overexpression of noggin increases oligodendrogenesis (Gomes et al 2003b).…”

Intrinsic and extrinsic regulation of the proliferation and differentiation of cells in the rodent rostral migratory stream

“…Furthermore, Li et al (1998) suggested that, in explant cultures of the telencephalic VZ, BMP4 treatment increases the number of TuJ1(ϩ) cells within the VZ. However, in cultured progenitor cells from the postnatal SVZ adjacent to the striatum, BMP2 and BMP7 lead to the cessation of cell proliferation and induction of astrocyte differentiation (Gross et al, 1996;Zhu et al, 1999a). More recent studies have shown that, in mouse hybridoma cells, BMPs also act directly on the CKI p21 CIP1 (Yamato et al, 2000) to induce apoptosis or cell cycle exit.…”

In vitro growth and differentiation of canine olfactory bulb-derived neural progenitor cells under variable culture conditions

“…NPC response to growth factors can vary with developmental stage, the factors used, and their concentration (Whittemore et al, 1999;Zhu et al, 1999). For example, although NPCs grown in either EGF or bFGF with heparin are multipotential, studies show a preferential gliogenic effect from EGF-derived cultures and an increased capacity for neuronal differentiation in cultures derived from bFGF and heparin, (Whittemore et al, 1999;Zhu et al, 1999). Combining EGF with bFGF and heparin produces a synergistic effect on NPC cultures (Caldwell and Svendsen, 1998;Vescovi et al, 1999;Gritti et al, 1999;Caldwell et al, 2004).…”

“…Culture conditions can also affect cell migration. Epidermal growth factor generated NPCs migrate further on a poly-D-lysine substrate (PDL) than bFGF generated NPCs (Zhu et al, 1999). Similarly, the substrate on which NPCs are grown can also affect cell growth and some functions; fibronectin and laminin enhance neurosphere motility and migration, whereas chondroitin sulfate proteoglycan inhibits sphere migration and velocity (Kearns et al, 2003).…”