Hox11L1 Expression by Precursors of Enteric Smooth Muscle: An Alternative Explanation for Megacecum in Hox11L1-I- Mice.

Autor: Kapur, P., Clarke, Christine M., Doggett, Barbara, Taylor, Brian E., Baldessari, Audrey, Parisi, Melissa A., Howe, Douglas G.
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Zdroj: Pediatric & Developmental Pathology; Mar/Apr2005, Vol. 8 Issue 2, p148-161, 14p
Abstrakt: Previous studies have focused on expression of Hoxl ILl in enteric neurons as the explanation loi" intestinal and uiinai bladder dysniotilily observed in mice that do not have the transcription factor. However", Ho\I loll is also expressed transiently in endo-, mcso-, and ectodermai cells of the most caudal embryo during gastrulation. We sought to more fully eharaeterize the fates of these cells because they might help explain the pathogenesis of lethal pseudo-obstruction in HoxllLl-nulI mice. The Cre recombinase cDNA was introduced into the Hoxl ILl locus, and expression of the "knock-in" allele was used to activate the Rosa26R, P-galactosidase reporter gene in cells with ongoing Hoxl ILl transcription and their descendants. During gastrulation, Rosa26R activation was observed in progenitors of caudal somatic and visceral ceils, including enteric smooth muscle. Expression in enteric neural precursors appeared much later. Analysis of endogenous Hoxl 1 LI mRNA in ancuronal segments of large intestine that were grafted under the ix-nai capsule indicated that the early activation of Hox 11L1 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 Hoxl ILl to include activation of an as yet unknown developmental program in visceral smooth muscle and allow the possibility that intestinal dysmotility in HoxllLI-null animals may not be a primary neural disorder. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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