Innervation of the esophagus in mice that lack MASH1

The striated muscle of the esophagus differs from other striated muscle, be cause it develops by the transdifferentiation of smooth muscle, and the mot or end plates receive a dual innervation from vagal (cholinergic) motor neu rons and nitric oxide synthase (NOS)containing enteric neurons. Mash1 -/- m ice have no enteric neurons in their esophagus and die within 48 hours of b irth without milk in their stomachs (Guillemot et al. [1993] Cell 75:463-47 6). In this study, the innervation of the esophagus of newborn Mash1 -/-, M ash1 +/- and wild type mice was examined. There was no difference between M ash1 -/-,Mash1 +/-, and wild type mice in the transdifferentiation of the m uscle and the development of nicotinic receptor clusters. However, there we re significantly more cholinergic nerve terminals per motor end plate in Ma sh1 -/- mice than Mash1 +/- or wild type mice. Each of the Mash1 -/- mice h ad fewer than 50 NOS neurons per esophagus, compared with approximately 3,0 00 in wild type mice. Newborn Mash1 +/- mice also contained significantly f ewer NOS neurons than wild type mice. In Mash1 -/- mice, NOS nerve fibers w ere virtually absent from the external muscle but were present at the myent eric plexus. Unlike that of newborn wild type mice, the lower esophageal sp hincter of Mash1 -/- mice lacked NOS nerve fibers; this may explain the abs ence of milk in the stomach. We conclude that 1) the transdifferentiation o f the esophageal muscle and the development of the extrinsic innervation do not require enteric neurons or MASH1, 2) extrinsic NOS neurons only innerv ate the myenteric plexus. (C) 1999 Wiley-Liss, Inc.