GDNF Is a Chemoattractant for Enteric Neural Cells

Abstract

In situ hybridization revealed that GDNF mRNA in the mid- and hindgut mesenchyme of embryonic mice was minimal at E10.5 but was rapidly elevated at all gut regions after E11, but with a slight delay (0.5 days) in the hindgut. GDNF mRNA expression was minimal in the mesentery and in the pharyngeal and pelvic mesenchyme adjacent to the gut. To examine the effect of GDNF on enteric neural crest-derived cells, segments of E11.5 mouse hindgut containing crest-derived cells only at the rostral ends were attached to filter paper supports and grown in catenary organ culture. With GDNF (100 ng/ml) in the culture medium, threefold fewer neurons developed in the gut explants and fivefold more neurons were present on the filter paper outside the gut explants, compared to controls. Thus, in controls, crest-derived cells colonized the entire explant and differentiated into neurons, whereas in the presence of exogenous GDNF, most crest-derived cells migrated out of the gut explant. This is consistent with GDNF acting as a chemoattractant. To test this idea, explants of esophagus, midgut, superior cervical ganglia, paravertebral sympathetic chain ganglia, or dorsal root ganglia from E11.5-E12.5 mice were grown on collagen gels with a GDNF-impregnated agarose bead on one side and a control bead on the opposite side. Migrating neural cells and neurites from the esophagus and midgut accumulated around the GDNF-impregnated beads, but neural cells in other tissues showed little or no chemotactic response to GDNF, although all showed GDNF-receptor (Ret and GFRalpha1) immunoreactivity. We conclude that GDNF may promote the migration of crest cells throughout the gastrointestinal tract, prevent them from straying out of the gut (into the mesentery and pharyngeal and pelvic tissues), and promote directed axon outgrowth.

Long‐distance cue from emerging dermis stimulates neural crest melanoblast migration

“…Long-range cues may characterize other neural crest paths as well. The otic placode may attract hindbrain neural crest cells (Sechrist et al, 1994); FGF-2 may be chemotactic in the mouse mesencephalon (Kubota and Ito, 2000); GDNF is chemoattractive to the enteric neural crest (Young et al, 2001). In the somite, both crest cells and axons preferentially enter the anterior sclerotome (Keynes and Stern, 1984;Rickmann et al, 1985), which can attract sensory and motor axons from a distance (Hotary and Tosney, 1996), suggesting that the anterior sclerotome may attract crest cells as well.…”

GDNF/Ret signaling and the development of the kidney

“…(54,87) This idea is supported by a number of observations, such as the ability of GNDF beads to apparently attract the growth of ectopic UBs from the Wolffian duct; (21,30,52) the migration of cultured Ret-expressing cells towards a source of GDNF, (78) a role of GDNF in pathfinding by the pronephric duct of the axolotl (88) and as a chemoattractant for migrating enteric neural crest cells. (89,90) As discussed above, it is clear that the expression domain of GDNF provides positional information that helps to determine the site of outgrowth of the primary UB from the WD. It is thus an appealing idea that the same process might continue to be important for determining the pattern of growth and branching at later stages of kidney development.…”

Developmental changes in neurite outgrowth responses of dorsal root and sympathetic ganglia to GDNF, neurturin, and artemin

“…Similarly, GDNF family members including artemin, GDNF, and neurturin appear to play a role in promoting neurite and axon outgrowth from some types of neurons (Ebendal et al, 1995;Bilak et al, 1999;Hashino et al, 1999Hashino et al, , 2001Schafer and Mestres, 1999;Andres et al, 2001;Enomoto et al, 2001;Young et al, 2001;Honma et al, 2002;Tollet et al, 2002). Axon outgrowth and cell migration are similar processes (Rakic, 1999); therefore, it is not unexpected that artemin and GDNF can also influence the migration of some neural precursors (Nishino et al, 1999;Enomoto et al, 2001;Young et al, 2001;Honma et al, 2002;Tollet et al, 2002) and other GFL-responsive cells such as kidney epithelial cells (Tang et al, 1998).…”