Background: Development of the enteric nervous system (ENS) requires interactions between migrating neural crest cells and the nascent gastrointestinal tract that are dependent upon genes expressed by both cell compartments. Hlx, a homeobox transcription factor gene that is expressed in mouse intestinal and hepatic mesenchyme, is required for normal embryonic growth of intestine and liver, and the Hlx-/- genotype is embryonic lethal. We hypothesized that Hlx is required for ENS development.
Results: Enteric neurons were identified in Hlx+/+ and Hlx-/- mouse embryos by immunostaining of embryo sections for the neural markers PGP9.5 and Phox2b, or by staining for beta-galactosidase in whole-mount embryos containing the dopamine beta-hydroxylase-nLacZ transgene. In Hlx+/+ embryos, neural crest cells/enteric neurons have moved from the stomach into the intestine by E10.5. By contrast, neural crest cells/enteric neurons remain largely restricted to the lateral stomach mesenchyme of Hlx-/- embryos, with only a few scattered neural crest cells/enteric neurons in the intestine between E10.5-16.5.
Conclusion: The Hlx homeobox transcription factor is required for early aspects of ENS development.
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http://dx.doi.org/10.1186/1471-213X-6-33 | DOI Listing |
Front Mol Neurosci
December 2024
Department of Surgery, University of Virginia, Charlottesville, VA, United States.
Introduction: Dysfunction of the enteric nervous system (ENS) is linked to a myriad of gastrointestinal (GI) disorders. Piezo1 is a mechanosensitive ion channel found throughout the GI tract, but its role in the ENS is largely unknown. We hypothesize that Piezo1 plays an important role in the growth and development of the ENS.
View Article and Find Full Text PDFDev Biol
January 2025
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA. Electronic address:
While the enteric nervous system (ENS) of jawed vertebrates is largely derived from the vagal neural crest, lamprey are jawless vertebrates that lack the vagal neural crest, yet possess enteric neurons derived from late-migrating Schwann cell precursors. To illuminate homologies between the ENS of jawed and jawless vertebrates, here we examine the diversity and distribution of neuronal subtypes within the intestine of the sea lamprey during late embryonic and ammocete stages. In addition to previously described 5-HT-immunoreactive serotonergic neurons, we identified NOS and VIP neurons, consistent with motor neuron identity.
View Article and Find Full Text PDFPLoS One
January 2025
Ionis Pharmaceuticals, Inc., Carlsbad, CA, United States of America.
Lateral Meningocele Syndrome (LMS), a disorder associated with NOTCH3 pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia that is ameliorated by the administration of Notch3 antisense oligonucleotides (ASO) targeting either Notch3 or the Notch3 mutation. To determine the consequences of LMS pathogenic variants in human cells and whether they can be targeted by ASOs, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a NOTCH36692-93insC insertion were created.
View Article and Find Full Text PDFInt J Radiat Biol
January 2025
Departamento de Biología Celular, Universidad de Sevilla, Seville, Spain.
Purpose: A substantial proportion of children with high risk Neuroblastoma die within the first 5 years post-diagnosis despite the complex treatment applied. In the recent years, tumor environment has been revealed as key factor for cancer treatment efficacy. In this sense, non-tumorigenic Neural Crest progenitor cells from high risk patients, have been described as part of Neuroblastoma stroma, promoting tumor growth and contributing to mesenchyme formation.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
Division of Cardiology, Department of Medicine, University of Washington (S.S., S.J., N.S., C.Y.L., L.L., D.A.D.).
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