Smooth-muscle-specific expression of neurotrophin-3 in mouse embryonic and neonatal gastrointestinal tract

Abstract

Vagal gastrointestinal (GI) afferents are essential for the regulation of eating, body weight, and digestion. However, their functional organization and the way that this develops are poorly understood. Neurotrophin-3 (NT-3) is crucial for the survival of vagal sensory neurons and is expressed in the developing GI tract, possibly contributing to their survival and to other aspects of vagal afferent development. The identification of the functions of this peripheral NT-3 thus requires a detailed understanding of the localization and timing of its expression in the developing GI tract. We have studied embryos and neonates expressing the lacZ reporter gene from the NT-3 locus and found that NT-3 is expressed predominantly in the smooth muscle of the outer GI wall of the stomach, intestines, and associated blood vessels and in the stomach lamina propria and esophageal epithelium. NT-3 expression has been detected in the mesenchyme of the GI wall by embryonic day 12.5 (E12.5) and becomes restricted to smooth muscle and lamina propria by E15.5, whereas its expression in blood vessels and esophageal epithelium is first observed at E15.5. Expression in most tissues is maintained at least until postnatal day 4. The lack of colocalization of β-galactosidase and markers for myenteric ganglion cell types suggests that NT-3 is not expressed in these ganglia. Therefore, NT-3 expression in the GI tract is largely restricted to smooth muscle at ages when vagal axons grow into the GI tract, and when vagal mechanoreceptors form in smooth muscle, consistent with its role in these processes and in vagal sensory neuron survival.

Mechanism of hyperphagia contributing to obesity in brain-derived neurotrophic factor knockout mice

“…β-galactosidase staining was also observed in the intestinal mucosa at E17 (Figure 1D,E). This staining may have reflected the presence of endogenous β-galactosidase as previously described at E17 and postnatal day 4 (Fox and McAdams, 2010), although some likely represents recombination as it occurred in these tissues at younger ages, prior to the appearance of endogenous enzyme (e.g., stomach epithelium; Figure 1A). Importantly, no β-galactosidase expression was detected in brain parenchyma at any of the embryonic ages examined, whereas it was present in a small number of adult brain regions by 2 months of age (illustrated for offspring of SM22α cre mice and BDNF lox reporter mice; see below).…”

Chronic Stress Induces Neurotrophin-3 in Rat Submandibular Gland

“…Hence, although NT-3 mRNA and protein levels increased in the submandibular gland during chronic stress, this did not seem to significantly contribute to the increased plasma NT-3 levels. Expression of NT-3 has been investigated in several other organs, including heart, lung, liver, pancreas, and stomach,33,38-41 however, there have been no previous reports that examined the mechanism by which NT-3 increases under stress conditions. Several studies have shown that increased levels of monoaminergic neurotransmitters, including adrenaline, noradrenaline, serotonin, and dopamine, induce BDNF expression in the brain under stress conditions 42-44.…”

Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation

“…First, expression of Cre recombinase in SM22α cre mice is largely restricted to smooth muscle, the main GI tissue that expresses NT-3 (33, 34, 36, 57). Second, tests with a Cre-dependent reporter strain provided evidence of high recombination efficiency in smooth muscle (34, 57).…”

“…NT-3 expression in the majority of developing GI organs is largely restricted to smooth muscle cells comprising the outer layers of the developing stomach, cecum, small and large intestines, and the walls of blood vessels that supply the GI tract (33, 36). However, each organ exhibits a unique expression pattern.…”