Dlx1/2 mice have abnormal enteric nervous system function.
Development
Embryonic development
Neurodevelopment
Neuroscience
Transcription
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
27 02 2020
27 02 2020
Historique:
received:
08
07
2019
accepted:
22
01
2020
pubmed:
6
2
2020
medline:
27
5
2021
entrez:
5
2
2020
Statut:
epublish
Résumé
Decades ago, investigators reported that mice lacking DLX1 and DLX2, transcription factors expressed in the enteric nervous system (ENS), die with possible bowel motility problems. These problems were never fully elucidated. We found that mice lacking DLX1 and DLX2 (Dlx1/2-/- mice) had slower small bowel transit and reduced or absent neurally mediated contraction complexes. In contrast, small bowel motility seemed normal in adult mice lacking DLX1 (Dlx1-/-). Even with detailed anatomic studies, we found no defects in ENS precursor migration, or neuronal and glial density in Dlx1/2-/- or Dlx1-/- mice. However, RNA sequencing of Dlx1/2-/- ENS revealed dysregulation of many genes, including vasoactive intestinal peptide (Vip). Using immunohistochemistry and reporter mice, we then found that Dlx1/2-/- mice have reduced VIP expression and fewer VIP-lineage neurons in their ENS. Our study reveals what we believe is a novel connection between Dlx genes and Vip and highlights the observation that dangerous bowel motility problems can occur in the absence of easily identifiable ENS structural defects. These findings may be relevant for disorders like chronic intestinal pseudo-obstruction (CIPO) syndrome.
Identifiants
pubmed: 32017713
pii: 131494
doi: 10.1172/jci.insight.131494
pmc: PMC7101142
doi:
pii:
Substances chimiques
Distal-less homeobox proteins
0
Homeodomain Proteins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : F30 DK117546
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK087715
Pays : United States
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