Related Experiment Video
Updated: Dec 29, 2025
Immunostaining to Visualize Murine Enteric Nervous System Development
Published on: April 29, 2015
Dlx1/2 mice have abnormal enteric nervous system function
Christina M Wright1,2, James P Garifallou3,2, Sabine Schneider1,2
1Department of Pediatrics.
Abstract:
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.
Insights
Mice lacking DLX1 and DLX2 transcription factors exhibit bowel motility issues due to reduced VIP-expressing neurons, even without structural defects in the enteric nervous system (ENS). This highlights a new link between DLX genes and VIP, relevant to motility disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Gastroenterology
Background:
- DLX1 and DLX2 are transcription factors crucial for the enteric nervous system (ENS).
- Previous studies noted potential bowel motility problems in mice lacking DLX1/2, but these were not fully understood.
- The precise role of DLX1/2 in ENS function and motility remained unclear.
Purpose of the Study:
- To investigate the functional consequences of DLX1/2 deficiency on small bowel motility.
- To elucidate the underlying molecular mechanisms, particularly the role of vasoactive intestinal peptide (VIP).
- To determine if structural ENS defects are present in DLX1/2 deficient mice.
Main Methods:
- Comparative analysis of small bowel transit and motility in wild-type, Dlx1/2-/-, and Dlx1-/- mice.
- Detailed anatomical studies of the ENS, including precursor migration and neuronal/glial density.
- RNA sequencing of the ENS from Dlx1/2-/- mice to identify gene dysregulation.
- Immunohistochemistry and reporter mice to assess VIP expression and VIP-lineage neurons.
Main Results:
- Dlx1/2-/- mice displayed significantly slower small bowel transit and impaired neurally mediated contraction complexes.
- No anatomical defects in ENS precursor migration or neuronal/glial density were observed in Dlx1/2-/- or Dlx1-/- mice.
- RNA sequencing revealed dysregulation of genes including VIP in Dlx1/2-/- ENS; confirmed by reduced VIP expression and fewer VIP-lineage neurons.
Conclusions:
- DLX1/2 transcription factors are essential for normal small bowel motility, independent of gross ENS structural defects.
- A novel link exists between DLX genes and the regulation of VIP expression and VIP-neuron development in the ENS.
- These findings offer insights into motility disorders like chronic intestinal pseudo-obstruction (CIPO).
