Development of the Enteric Nervous System in Relation to Hirschsprung's Disease

Young, Heather M.; Newgreen, Donald F.; Burns, Alan J.

doi:10.1002/9780470090121.ch11

Cited by 5 publications

(6 citation statements)

References 218 publications

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“…During embryonic development NCC are initially specified, they then undergo epithelial–mesenchymal transition, delaminate from the neural folds, and extensively migrate and proliferate 5 in order to colonize the entire length of the gut and differentiate into a wide range of neuronal phenotypes and glial cells. A number of transcription factors (including Phox2b, Sox10, Pax3, Mash1, Hox11L1 and Sip1), signalling pathways (Ret/Gfrα1/Gdnf and endothelin receptor‐B/endothelin‐3), neurotrophins and growth factors, neuronal and axon guidance molecules, and other molecules, are now known to be necessary for ENS formation (reviewed in Refs 6,7). The result of the complex inter‐related developmental events governed by such mechanisms is that a relatively small number of NC‐derived precursor cells ultimately give rise to an extensive and functional ENS believed to contain more neurons than the spinal cord 1,8 …”

Section: Introductionmentioning

confidence: 99%

Inhibition of cell death results in hyperganglionosis: implications for enteric nervous system development

Wallace¹,

Barlow²,

Navaratne³

et al. 2009

Neurogastroenterology Motil

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The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells (NCC) that delaminate from the neural tube and undergo extensive migration and proliferation in order to colonize the entire length of the gut and differentiate into many millions of neurons and glial cells. Although apoptotic programmed cell death is an essential physiological process during development of the majority of the vertebrate nervous system, apoptosis within early ENS development has not been comprehensively investigated. The aim of this study was to determine the presence and extent of apoptosis within the vagal NCC population that gives rise to most of the ENS in the chick embryo. We demonstrated that apoptotic cells, as shown by terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling and active caspase-3 immunoreactivity, are present within an electroporated green fluorescent protein (GFP) and human natural killer-1 (HNK-1) immunopositive NCC population migrating from the vagal region of the neural tube to the developing foregut. Inhibition of caspase activity in vagal NCC, by electroporation with a dominant-negative form of caspase-9, increased the number of vagal NCC available for ENS formation, as shown by 3-dimensional reconstruction of serial GFP or HNK-1 labelled sections, and resulted in hyperganglionosis within the proximal foregut, as shown by NADPH-diaphorase whole gut staining. These findings suggest that apoptotic cell death may be a normal process within the precursor pool of pre-enteric NCC that migrates to the gut, and as such it may play a role in the control of ENS formation.

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Section: Introductionmentioning

confidence: 99%

Inhibition of cell death results in hyperganglionosis: implications for enteric nervous system development

Wallace¹,

Barlow²,

Navaratne³

et al. 2009

Neurogastroenterology Motil

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“…Our findings also highlight intrinsic differences, not only in the absolute numbers of somite 3 NCC, but also in their increased capacity for proliferation in vivo, properties that could underlie the ability of this specific NCC population, and not other more rostral vagal NCC populations, to form the entire ENS. The inability of NCC to colonise the entire gastrointestinal tract is the cause of Hirschsprung's disease (HSCR) in humans (Brooks et al, 2005;Swenson, 2002;Young et al, 2006), and mutations in a number of different genes in rodents have been shown to phenocopy this disease. More specifically, animals carrying monoisoformic alleles of the receptor tyrosine kinase gene Ret (Ret…”

Section: Research Articlementioning

confidence: 99%

“…Colonisation of the entire length of the gut by NCC is essential for the development of the ENS, as absence of enteric ganglia in the hindgut has been associated with Hirschsprung's disease (HSCR) in humans (Brooks et al, 2005;Swenson, 2002;Young et al, 2006) and aganglionic megacolon in rodents (for reviews, see Burns and Thapar, 2006;Gershon, 1999;Young et al, 2006). Therefore, any understanding of the processes that regulate NCC colonisation of the gut will further our knowledge of disease pathogenesis and may advance potential treatments for gut aganglionosis.…”

Section: Introductionmentioning

confidence: 99%

Critical numbers of neural crest cells are required in the pathways from the neural tube to the foregut to ensure complete enteric nervous system formation

Barlow¹,

Wallace²,

Thapar³

et al. 2008

Development

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The enteric nervous system (ENS) is mainly derived from vagal neural crest cells (NCC) that arise at the level of somites 1-7. To understand how the size and composition of the NCC progenitor pool affects ENS development, we reduced the number of NCC by ablating the neural tube adjacent to somites 3-6 to produce aganglionic gut. We then back-transplanted various somite lengths of quail neural tube into the ablated region to determine the 'tipping point', whereby sufficient progenitors were available for complete ENS formation. The addition of one somite length of either vagal, sacral or trunk neural tube into embryos that had the neural tube ablated adjacent to somites 3-6, resulted in ENS formation along the entire gut. Although these additional cells contributed to the progenitor pool, the quail NCC from different axial levels retained their intrinsic identities with respect to their ability to form the ENS; vagal NCC formed most of the ENS, sacral NCC contributed a limited number of ENS cells, and trunk NCC did not contribute to the ENS. As one somite length of vagal NCC was found to comprise almost the entire ENS, we ablated all of the vagal neural crest and back-transplanted one somite length of vagal neural tube from the level of somite 1 or somite 3 into the vagal region at the position of somite 3. NCC from somite 3 formed the ENS along the entire gut, whereas NCC from somite 1 did not. Intrinsic differences, such as an increased capacity for proliferation, as demonstrated in vitro and in vivo, appear to underlie the ability of somite 3 NCC to form the entire ENS.

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“…To colonise the gut and form a functional ENS, NCC must undergo a number of key processes, including migration, survival, proliferation, differentiation, and axon formation. A large number of transcription factors, signalling pathways, and neurotrophic factors are involved in controlling the processes underlying normal ENS development, some of which are summarised in Figure 1; however, a detailed description of these molecular mechanisms is beyond the scope of this article and they are comprehensively reviewed elsewhere (9)(10)(11)(12).…”

Section: Embryologic Development Of the Ensmentioning

confidence: 99%