Colonization of the bowel by the precursors of enteric glia: Studies of normal and congenitally aganglionic mutant mice

Abstract

The terminal portion of the ls/ls mouse is congenitally aganglionic because the precursors of enteric neurons fail to enter this region. This animal was studied in order to gain insight into the origin of enteric glia and into the process by which the precursors of these cells colonize the gut. In control (CD-1) mice, immunoreactivity of the glial marker, glial fibrillary acidic protein, appeared for the first time in the fetal bowel at day E16 and, in adults, was much more intense within intraenteric neural elements than in nerves outside the bowel. Glial fibrillary acidic protein developed in tissue cultures of fetal intestine explanted before the protein appeared in situ, and before the bowel became innervated by extrinsic nerves; thus, the precursors of cells able to elaborate glial fibrillary acidic protein must have been present, but unrecognizable, in the original explants. This explant assay demonstrated that these glial precursors were present in all regions of the bowel of control mice, but not in the presumptive aganglionic bowel of ls/ls mice. The nerves (of extrinsic origin) in the aganglionic tissue of ls/ls mice showed a high level of immunoreactive glial fibrillary acidic protein; nevertheless, their ultrastructure was typical of peripheral nerve, not enteric plexus, and they contained Schwann cells, not enteric glia. These observations support the view that enteric glia are derived from the single wave of neural crest colonists that populates the enteric nervous system before the gut receives its extrinsic innervation. These glial precursors, like neuronal precursors, tend to be excluded from the presumptive aganglionic ls/ls bowel. In contrast, Schwann cells grow into the abnormal ls/ls gut with the extrinsic innervation. The enteric microenvironment appears to promote the expression of glial fibrillary acidic protein in both enteric glia and Schwann cells; however, even within the bowel, Schwann cells retain their characteristic morphology. It is thus probable that the normal enteric nervous system contains supporting cells of separate lineages, enteric glia and Schwann cells.

Appearance of neurons and glia with respect to the wavefront during colonization of the avian gut by neural crest cells

“…Our study confirms the observations of Balaskas and Gabella (1998), who first reported the presence of GFAP-IR in the chick gut at early stages of development. Others have also observed GFAP-IR at late stages in the development of the chick (Payette et al, 1984) and mouse (Rothman et al, 1986). Recent observations indicate that glial markers may appear earlier in the mouse gut but still well behind the wavefront (H. Young, personal communication).…”

Neural and skin cell‐specific expression pattern conferred by steel factor regulatory sequence in transgenic mice

“…Precursors of these cells are known to reach developing gut at as early as 9 to 10 dpc (Rothman et al, 1986) and at around 12.5 dpc lacZ expressing cells appeared. This suggests that neural crest precursors develop to produce SLF after reaching the developing gut.…”

Role of enteric glial cells in inflammatory bowel disease

“…These cells colonize the mouse embryonic gut at E9.0 and, when cultured in vitro, give rise to both neurons and glial cells (Rothman et al, 1986). However, during development, enteric neurons appear prior to EGCs as evidenced by the detection of specific markers for both cell types (Rothman and Gershon, 1982;Rothman et al, 1986), and the intrinsic and environmental signals involved in the commitment of precursor cells in the neuronal or glial lineages remain to be elucidated.…”

“…EGCs could therefore contribute to the development of the enteric neuronal network (Bä r et al, 1997;Gershon, 1999) and to neuroprotection. However, EGCs are not the primary source of GDNF in the developing gut as GDNF is expressed as early as E9.0 in the mouse gut (Hellmich et al, 1996), although differentiated EGCs first appear at E16 (Rothman et al, 1986).…”