Abstract
Previous studies have focused on expression of Hox11L1 in enteric neurons as the explanation for intestinal and urinary bladder dysmotility observed in mice that do not have the transcription factor. However, Hox11L1 is also expressed transiently in endo-, meso-, and ectodermal cells of the most caudal embryo during gastrulation. We sought to more fully characterize the fates of these cells because they might help explain the pathogenesis of lethal pseudo-obstruction in Hox11L1-null mice. The Cre recombinase cDNA was introduced into the Hox11L1 locus, and expression of the “knock-in” allele was used to activate the Rosa26R, β-galactosidase reporter gene in cells with ongoing Hox11L1 transcription and their descendants. During gastrulation, Rosa26R activation was observed in progenitors of caudal somatic and visceral cells, including enteric smooth muscle. Expression in enteric neural precursors appeared much later. Analysis of endogenous Hox11L1 mRNA in aneuronal segments of large intestine that were grafted under the renal capsule indicated that the early activation of Hox11L1 in visceral mesoderm was transient and ceased before colonization of the large intestine by neural progenitors. Mice homozygous for the Cre allele died shortly after weaning, with cecal and proximal colonic distention but without overt anatomic defects that might represent maldevelopment of the visceral mesoderm. Our findings expand the range of possible functions of Hox11L1 to include activation of an as yet unknown developmental program in visceral smooth muscle and allow the possibility that intestinal dysmotility in Hox11L1-null animals may not be a primary neural disorder.
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Acknowledgments
The authors thank Drs. G. Stanley McKnight and Richard Palmiter for mentorship. This work was supported by the National Institutes of Health (RO1 DK61194), the Center for Ecogenetics and Environmental Health at the University of Washington (NIEHS P30 ES07033), the Howard Hughes Medical Institute (postdoctoral support for M.A.P.), and the Environmental Pathology/Toxicology Training Program (NIEHS 5 T32 ES07032, postdoctoral support for A.B.).
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Kapur, R.P., Clarke, C.M., Doggett, B. et al. Hox11L1 Expression by Precursors of Enteric Smooth Muscle: An Alternative Explanation for Megacecum in Hox11L1 −/− Mice. Pediatr Dev Pathol 8, 148–161 (2005). https://doi.org/10.1007/s10024-005-1126-0
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DOI: https://doi.org/10.1007/s10024-005-1126-0