Mitogenic and anti‐proliferative signals for neural crest cells and the neurogenic action of TGF‐β1

Abstract

The influence of pertinent growth factors on proliferation and differentiation of quail neural crest cell was assessed by in vitro colony assay in a serum-free (0.5% chick embryo-extract supplemented) culture medium. The factors tested included basic fibroblast growth factor (bFGF; FGF-2), neurotrophins, and transforming growth factor-beta-1 (TGF-b). Both bFGF and neurotrophins are implicated in the development of the peripheral nervous system, whereas TGF-b can affect cell differentiation and modulate the action of other growth factors. Bromodeoxyuridine (BrdU) incorporation indicated that bFGF is mitogenic to pluripotent neural crest cells (and/or their immediate progeny) and to committed melanogenic cells. However, this was not reflected in an increase in colony size. In contrast, colony size did increase when nerve growth factor (NGF) was present in addition to bFGF. This indicated either that both factors are required to initiate cell proliferation or that at least some bFGF-exposed cells become dependent on neurotrophins for survival. Sequential addition of the factors showed that exposure to bFGF was required prior to the presence of a neurotrophin, thus favoring the latter possibility. All three neurotrophins tested, NGF, brainderived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), were capable of supporting survival of pluripotent neural crest cells (or their closely related progeny) in the presence of bFGF. In the absence of bFGF, neurotrophins did not affect colony size. Although the BrdU data indicated that bFGF is also a mitogen for committed melanogenic cells, the size of pigmented colonies did not change in the presence of bFGF alone or of bFGF plus a neurotrophin. This suggested that another, yet to be determined, factor is required for the survival of proliferating melanogenic cells.

Cardiac neural crest stem cells

“…NET mRNA levels are regulated synergistically by autocrine NT-3, transforming growth factor-␤1 (TGF-␤1), and fibroblast growth factor-2 (FGF-2) action (Zhang et al, 1997a;Ren et al, 2001). Quail and mouse neural crest cells express NET protein even before onset of their emigration from the neural tube (Ren et al, 2003).…”

Induction of neurogenin‐1 expression by sonic hedgehog: Its role in development of trigeminal sensory neurons

“…As described above, BMP-4 is implicated in the specification of autonomic neurons. FGF-2 promotes the proliferation of neural crest cells (Murphy et al, 1994;Zhang et al, 1997;Sieber-Blum and Zhang, 1997;Sieber-Blum, 1998) and regulates their migration (Kubota and Ito, 2000). FGF-8 affects not only midbrain development (Crossley et al, 1996;Lee et al, 1997) but also neural crest cell migration (Kubota and Ito, 2000).…”

“…Although FGF-2 promotes the proliferation of neural crest cells, this signaling molecule inhibits differentiation into neurons (Murphy et al, 1994;Zhang et al, 1997;Sieber-Blum and Zhang, 1997;Sieber-Blum, 1998). FGF-2 promotes chondrogenesis and skeletogenesis of cranial neural crest cells ( Sarkar et al, 2001;Petiot et al, 2002).…”

Neurotrophin‐3 signaling in mammalian Merkel cell development

“…The leading edge of the dorsolaterally migrating neural crest cell population contains pluripotent stem cells that are able to give rise to a variety of neural crest derivatives Richardson and Sieber-Blum, 1993). NT-3, as well as BDNF and NGF support the survival of proliferating neural crest stem cells and their immediate progeny, suggesting that the neurotrophins act through the nonselective neurotrophin receptor, p75NTR (Zhang et al, 1997).…”