A second source of precursor cells for the developing enteric nervous system and interstitial cells of Cajal

Abstract

The enteric nervous system is believed to be derived solely from the neural crest cells. This is partly based on the belief that the neural crest cells are the sole neural tube-derived cells colonizing the gastrointestinal tract. However, recent studies have shown that after the emigration of neural crest cells an additional population of cells emigrate from the cranial neural tube. These cells originate in the ventral part of the hindbrain, emigrate through the site of attachment of the cranial nerves, and colonize a variety of developing structures including the gastrointestinal tract. This cell population has been named the ventrally emigrating neural tube (VENT) cells. We followed the fate of these cells in the gastrointestinal tract. Ventral hindbrain neural tube cells of chick embryos were tagged with replication-deficient retroviral vectors containing the LacZ gene, after the emigration of neural crest from this region. In control embryos, the viral concentrate was dropped on the dorsal part of the neural tube. Embryos were sacrificed from embryonic days 3-12 and processed for the detection of LacZ positive ventrally emigrating neural tube cells. These cells colonized only the foregut, specifically the duodenum and stomach. Immunostaining with the neural crest cell marker HNK-1 showed that they were HNK-1 negative, indicating that they were not derived from neural crest. Cells were detected in three locations: (1). the myenteric and submucosal plexus of the enteric nervous system; (2). circular smooth muscle cell layer; and (3). mucosal lining of the lumen. A variety of specific markers were used to identify their fate. Some ventrally emigrating neural tube cells differentiated into neurons and glial cells, indicating that the enteric nervous system in the foregut develops from an additional source of precursor cells. It was also found that some of these cells differentiated into interstitial cells of Cajal, which mediate impulses between the enteric nervous system and smooth muscle cells, whereas others differentiated into epithelium. Altogether, these results indicate that the ventrally emigrating neural tube cells are multipotential. More importantly, they reveal a novel source of precursor cells for the neurons and glial cells of the enteric nervous system. The developmental and functional significance of the heterogeneous origin of the cell types remains to be established.

Nestin‐expressing cells in the gut give rise to enteric neurons and glial cells

“…Sohal et al [34] followed a population of cells emigrating ventrally from the cranial neural tube in the developing chick and into the gastrointestinal tract. These cells colonized only the foregut and were located in enteric ganglia, smooth muscle, and mucosa.…”

Neural crest and placode interaction during the development of the cranial sensory system

“…In addition to neural crest cells that delaminate from the dorsal neural tube, another population of ventrally emigrating neural tube cells was postulated to contribute to the otic vesicle and cochleovestibular ganglion (Sohal et al, 2002; Ali et al, 2003a, 2003b). However, the labelling techniques utilised in these studies have been called into question (Boot et al, 2003) and retroviral infection and quail–chick chimeras led the authors to conclude that there is little evidence for the existence of these cells.…”

The importance of interstitial cells of cajal in the gastrointestinal tract

“…[1819] In the chick, some ICC in the stomach and duodenum may also develop from multipotent, ventrally emigrating neural tube cells. [20] In the small intestine of mice, ICC emerge from a population of Kit-positive precursor cells at about embryonic day 15. [21] Kit signaling is critical during the late gestational period and after birth for the development and maintenance of ICC populations.…”