Introduction

The enteric nervous system (ENS) is the largest and the most complex division of the peripheral nervous system 1 . The ENS contains more neurons than the spinal cord and is capable of mediating reflex activity in the absence of central nervous system. About 80-100 million enteric neurons can be classified into functional distinct subpopulations, including intrinsic primary neurons, inter-neurons, motor neurons, secretomotor and vasomotor neurons 2 . The ENS plays a crucial role in normal...

Contents

1 Hirschsprung's Disease A Historical Perspective 1691-2005 2 Development of the Enteric Nervous System 13 2.1 Introduction 2.2 Embryonic Origin of ENS 13 2.3 Origin and Development of Neural Crest-Derived Cells 2.4 Functional Development of the ENS 15 2.5 Development of Intestinal Motility 15 2.6 Genes Involved in ENS Development 15 2.7 Other Factors Implicated in the Control of ENS Development 2.8 Conclusions of the Enteric Nervous System 21 3.1 Introduction 21 3.2 The Normal Enteric Nervous...

Sip1

Ferentiation of neurons and neurite extension 41, 45, 46 . The RET receptor is the signaling component of receptor complexes with four ligands, glial derived neurotropic factor (GDNF), neurturin (NTN), artemin (ATM), and persephin (PSP) 45, 47 . The complete receptor complex includes the RET receptor tyrosine kinase and a glyco-sylphosphatidylinositol-anchored binding component (GFRal, GFRa2, GFRa3, and GFRa4) 47-49 . In vivo the absence of GDNF GFRal-mediated signaling leads to the failure of...

P Puri and U Rolle

2.1 Introduction 2.2 Embryonic Origin of ENS 13 2.3 Origin and Development of Neural Crest-Derived Cells 2.4 Functional Development of the ENS 15 2.5 Development of Intestinal Motility 15 2.6 Genes Involved in ENS Development 15 2.6.1 RET GDNF GFRa1 Signaling System 15 2.6.2 Endothelin Signaling Pathway 16 2.6.3 SOX10 2.6.4 PHOX2B 2.6.5 HOX11L1 2.7 Other Factors Implicated in the Control of ENS Development 2.8 Conclusions References

Preface

Hirschsprung's disease is one of the most important and most fascinating diseases in paediatric surgery. Our understanding of Hirschsprung's disease is developing rapidly, not only in relation to its pathophysiology and the development of new surgical techniques, but especially in relation to new genetic findings. A first comprehensive description of the pathophysiology, clinical symptoms, diagnosis and therapy of Hirschsprung's disease was outlined in 1970 by Theodor Ehrenpreis, Professor of...

The ENS is Derived from the Neural Crest

The first clear demonstration that the ENS is derived from the neural crest was made by Yntema and Hammond who noted that enteric ganglia fail to appear when the anterior neural crest is deleted in chick embryos 38, 39 . Their work was confirmed, and levels of the crest that contribute to the ENS were more precisely identified by Le Douarin and her colleagues 40, 41 . These investigators took advantage of the distinctive nucleolar-associ-ated heterochromatin of quail cells, which allows these...

The Normal Enteric Nervous System

The mature ENS is absolutely unique and different from any other region of the peripheral nervous system (PNS). First, the ENS is independent and can function in the absence of input from the brain or spinal cord 3, 4 . Second, in contrast to the remainder of the PNS, the ENS can mediate reflexes, even when it is isolated from the central nervous system (CNS). This ability of the ENS is often overlooked, even though it has long been known to be true. As the 19th Century turned to the 20th,...

Info

Her autopsy demonstrated dilatation of the colon and upper rectum that ceased abruptly 2 inches from the anus. No anal stricture or stenosis was observed 14 . This may have represented an instance of low segment Hirschsprung's disease. While a number of other physicians reported instances of severe constipation and colon dilatation in children that eventually led to their demise, Harald Hirschsprung, a Danish pediatrician from Queen Louise Children's Hospital, Copenhagen, presented the...

The Extracellular Matrix is Abnormal in the Presumptive Aganglionic Bowel of Isls Mice

A variety of defects involving components of the extracellular matrix have been found in ls ls mice 200-202 and in human patients with Hirschsprung's disease 203, 204 . A common feature that unites these abnormalities is that they all involve an over-abundance and or maldistribution of constituents of basal laminae. Molecules that have been noted to be over-abundant include laminin, collagen type IV, nidogen non-sulfated glycosaminogly-cans, and proteoglycans. In the developing colon of fetal...

Organization of Enteric Neurons

The ENS of most adult mammals is comprised of two major interconnected ganglionated plexuses, the submuco-sal and the myenteric 3, 4 . The submucosal plexus is the smaller of the two. In larger animals, including humans, the submucosal plexus can be divided into separate plexuses of Schabadasch (external) and Meissner (internal) 29 however, these plexuses interconnect extensively and clear functional distinctions are not yet known. The submucosal plexus is thus usually treated a single entity 4...

NT3 Promotes the Development of Enteric Neurons

A major breakthrough, which has enabled the effects of growth factors on the development of enteric neurons or glia to be studied in vitro, has been the development of a means of isolating crest-derived cells from within the wall of the fetal bowel. If crest-derived cells are not so isolated, then the direct actions of growth factors on crest-derived neural and or glial precursors cannot be distinguished from indirect effects of these molecules on other cells of the enteric mesenchyme. The...

References

Adamson WAD, Aird I 1932 Megacolon evidence in favor of a neurogenic origin. Br J Surg 20 220-223 2. Adson A 1937 Hirschsprung's disease indications for and results obtained by sympathectomy. Surgery 1 859-877 3. Albanese CT, Jennings RW, Smith B, Bratton B, Harrison MR 1999 Perineal one-stage pull-through for Hirschsprung's disease. J Pediatr Surg 34 377-380 4. Aslam A, Spicer RD, Corfield AP 1998 Turnover of radioactive mucin precursors inn the colon of patients with Hirschsprung's disease...