The Hlx Homeobox Transcription Factor is Required Early in Enteric Nervous System Development

Overview

Journal BMC Dev Biol

Publisher Biomed Central

Specialties Biology
Reproductive Medicine

Date 2006 Jul 21

PMID 16854219

Citations 10

Authors

Michael D Bates

Dana T Dunagan

Lynn C Welch

Ajay Kaul

Richard P Harvey

Affiliations

Soon will be listed here.

Abstract

Background: Development of the enteric nervous system (ENS) requires interactions between migrating neural crest cells and the nascent gastrointestinal tract that are dependent upon genes expressed by both cell compartments. Hlx, a homeobox transcription factor gene that is expressed in mouse intestinal and hepatic mesenchyme, is required for normal embryonic growth of intestine and liver, and the Hlx-/- genotype is embryonic lethal. We hypothesized that Hlx is required for ENS development.

Results: Enteric neurons were identified in Hlx+/+ and Hlx-/- mouse embryos by immunostaining of embryo sections for the neural markers PGP9.5 and Phox2b, or by staining for beta-galactosidase in whole-mount embryos containing the dopamine beta-hydroxylase-nLacZ transgene. In Hlx+/+ embryos, neural crest cells/enteric neurons have moved from the stomach into the intestine by E10.5. By contrast, neural crest cells/enteric neurons remain largely restricted to the lateral stomach mesenchyme of Hlx-/- embryos, with only a few scattered neural crest cells/enteric neurons in the intestine between E10.5-16.5.

Conclusion: The Hlx homeobox transcription factor is required for early aspects of ENS development.

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References

Lang D, Chen F, Milewski R, Li J, Lu M, Epstein J . Pax3 is required for enteric ganglia formation and functions with Sox10 to modulate expression of c-ret. J Clin Invest. 2000; 106(8):963-71. PMC: 314346. DOI: 10.1172/JCI10828. View

Kapur R, Clarke C, Doggett B, Taylor B, Baldessari A, Parisi M . Hox11L1 expression by precursors of enteric smooth muscle: an alternative explanation for megacecum in HOX11L1-/- mice. Pediatr Dev Pathol. 2005; 8(2):148-61. DOI: 10.1007/s10024-005-1126-0. View

Bates M . Development of the enteric nervous system. Clin Perinatol. 2002; 29(1):97-114. DOI: 10.1016/s0095-5108(03)00066-6. View

Young H, Bergner A, Muller T . Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine. J Comp Neurol. 2003; 456(1):1-11. DOI: 10.1002/cne.10448. View

Stewart A, Anderson R, Young H . Characterization of lacZ-expressing cells in the gut of embryonic and adult DbetaH-nlacZ mice. J Comp Neurol. 2003; 464(2):208-19. DOI: 10.1002/cne.10766. View

Sanes J, Rubenstein J, Nicolas J . Use of a recombinant retrovirus to study post-implantation cell lineage in mouse embryos. EMBO J. 1986; 5(12):3133-42. PMC: 1167303. DOI: 10.1002/j.1460-2075.1986.tb04620.x. View

Wolgemuth D, Behringer R, Mostoller M, Brinster R, Palmiter R . Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development. Nature. 1989; 337(6206):464-7. DOI: 10.1038/337464a0. View

Troy C, Brown K, Greene L, Shelanski M . Ontogeny of the neuronal intermediate filament protein, peripherin, in the mouse embryo. Neuroscience. 1990; 36(1):217-37. DOI: 10.1016/0306-4522(90)90364-a. View

Allen J, Lints T, Jenkins N, Copeland N, Strasser A, Harvey R . Novel murine homeo box gene on chromosome 1 expressed in specific hematopoietic lineages and during embryogenesis. Genes Dev. 1991; 5(4):509-20. DOI: 10.1101/gad.5.4.509. View

10.

Kent C, Clarke P . The immunolocalisation of the neuroendocrine specific protein PGP9.5 during neurogenesis in the rat. Brain Res Dev Brain Res. 1991; 58(1):147-50. DOI: 10.1016/0165-3806(91)90248-h. View

11.

MERCER E, Hoyle G, Kapur R, Brinster R, Palmiter R . The dopamine beta-hydroxylase gene promoter directs expression of E. coli lacZ to sympathetic and other neurons in adult transgenic mice. Neuron. 1991; 7(5):703-16. DOI: 10.1016/0896-6273(91)90274-4. View

12.

Kapur R, Hoyle G, MERCER E, Brinster R, Palmiter R . Some neuronal cell populations express human dopamine beta-hydroxylase-lacZ transgenes transiently during embryonic development. Neuron. 1991; 7(5):717-27. DOI: 10.1016/0896-6273(91)90275-5. View

13.

Sanes J, Johnson Y, Kotzbauer P, Mudd J, Hanley T, Martinou J . Selective expression of an acetylcholine receptor-lacZ transgene in synaptic nuclei of adult muscle fibers. Development. 1991; 113(4):1181-91. DOI: 10.1242/dev.113.4.1181. View

14.

Pham T, Gershon M, Rothman T . Time of origin of neurons in the murine enteric nervous system: sequence in relation to phenotype. J Comp Neurol. 1991; 314(4):789-98. DOI: 10.1002/cne.903140411. View

15.

Kapur R, Yost C, Palmiter R . A transgenic model for studying development of the enteric nervous system in normal and aganglionic mice. Development. 1992; 116(1):167-75. DOI: 10.1242/dev.116.Supplement.167. View

16.

Gershon M, Chalazonitis A, Rothman T . From neural crest to bowel: development of the enteric nervous system. J Neurobiol. 1993; 24(2):199-214. DOI: 10.1002/neu.480240207. View

17.

Guillemot F, Lo L, Johnson J, Auerbach A, Anderson D, Joyner A . Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons. Cell. 1993; 75(3):463-76. DOI: 10.1016/0092-8674(93)90381-y. View

18.

Gehring W, Affolter M, Burglin T . Homeodomain proteins. Annu Rev Biochem. 1994; 63:487-526. DOI: 10.1146/annurev.bi.63.070194.002415. View

19.

Tassabehji M, Newton V, Leverton K, Turnbull K, Seemanova E, Kunze J . PAX3 gene structure and mutations: close analogies between Waardenburg syndrome and the Splotch mouse. Hum Mol Genet. 1994; 3(7):1069-74. DOI: 10.1093/hmg/3.7.1069. View

20.

Horan G, Wu K, Wolgemuth D, Behringer R . Homeotic transformation of cervical vertebrae in Hoxa-4 mutant mice. Proc Natl Acad Sci U S A. 1994; 91(26):12644-8. PMC: 45495. DOI: 10.1073/pnas.91.26.12644. View