Identifying Components of Max Factor

Previews in vivo, whereas cutaneous targets innervated by other Identifying Components sensory neurons (the adjoining hyoid process or the of Max Factor forelimb bud) neither elicited nor directed early trigemi-nal axons (see figure). The diffusible trigeminal attrac-tant, coined Maxillary (Max) Factor, appeared to emanate from the target field epithelium, because when early How the complexity of neuronal interconnections be-trigeminal ganglia were cocultured with isolated maxil-comes established during development has intrigued lary epithelium and mesenchyme, the axons grew to-biologists ever since the neuron in its many elaborate ward the epithelium in a small percentage of cases but forms was recognized as the fundamental building block never toward the mesenchyme (Lumsden and Davies, of the nervous system. Although recent years have wit-1986). The demonstration that the early target-directed nessed remarkable progress in elucidating the mecha-growth was not affected by function-blocking antibodies nisms that guide axons to their targets and identifying to NGF showed that this activity was not due to this a number of the molecules involved (Tessier-Lavigne neurotrophin. and Goodman, 1996), barely two decades ago there was Although the collagen gel coculture paradigm paved little more than a plethora of hypotheses. One of the the way for the identification and cloning of the first most appealing of these, put forward by Ramon y Cajal bona fide diffusible axon guidance molecules, the net-in the last century, is that axons are guided to their rins (Serafini et al., 1994; Tessier-Lavigne et al., 1988), targets by gradients of specific, diffusible chemoattrac-the identity of Max Factor remained elusive. In this issue tants. This idea lay dormant until a series of experiments of Neuron, the identities of the molecules responsible in the late seventies showed that intracranial injection for this in vitro activity have been pinned down by O'Con-of Nerve Growth Factor (NGF) causes extensive growth nor and Tessier-Lavigne (1999). In a comprehensive set of sympathetic axons into the brain (Menesini-Chen et of carefully controlled experiments, they show that two al., 1978), and that sensory axons turn toward a source of neurotrophins that had not been cloned at the time when NGF in culture (Gundersen and Barrett, 1979). Although Max Factor activity was first identified—neurotrophin-3 these observations were widely interpreted as evidence (NT-3) and, to a lesser extent, Brain-Derived Neuro-that sympathetic and sensory axons are guided to their trophic Factor (BDNF)—can account for at least the neu-targets by gradients of target-derived NGF, the demon-rite growth-promoting activity …