title: Neuregulin 1 is involved in enteric nervous system development in zebrafish.
abstract: BACKGROUND
  Hirschsprung's disease (HD, also known as congenital colon aganglionosis) is a congenital disorder characterized by the absence of intramural ganglion cells in the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. Recent studies have indicated neuregulin 1 (NRG1) as a new candidate gene involved in the development of the enteric nervous system (ENS) in humans.
  
  
  METHODS
  In our study, we investigated the role of NRG1 in zebrafish ENS development by assessing NRG1 expression patterns during ENS development. Knockdown, overexpression and rescue zebrafish models of NRG1 were created to evaluate differences in phenotype, numbers of enteric neurons, ENS-related factors and nerve fiber arrangements.
  
  
  RESULTS
  NRG1 was expressed in zebrafish intestine at both the larval and adult stage. We also found that decreased expression of NRG1 resulted in reductions in enteric neuron number and decreased expression of ENS development markers. Moreover, NRG1-knockdown zebrafish exhibited a disordered arrangement of nerve fibers.
  
  
  CONCLUSIONS
  Collectively, these results demonstrated that NRG1 expression might play a role in zebrafish ENS development. In addition, by modulating NRG1 expression, we created a model that may be useful for investigating the mechanism underlying HD pathogenesis.
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: pujiarui2006@126.com.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: tshaotao83@126.com.
authors.forename: Shaotao
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: qs_tong@hotmail.com.
authors.forename: Qiangsong
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Gastrointetinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Guobin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Biology Science, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Biology Science, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Gastrointetinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Mei
mesh_terms: D000818:Animals; D017615:Enteric Nervous System / Q000473:pathology; D005769:Gastrointestinal Motility / Q000235:genetics; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D007422:Intestines / Q000473:pathology; D020890:Neuregulin-1 / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015027:Zebrafish / Q000235:genetics
chemical_list: C094131:NRG1 protein, human; D020890:Neuregulin-1
keywords: Development; Enteric nervous system; Neuregulin 1; Zebrafish