Notochordal and foregut abnormalities correlate with elevated neural crest apoptosis in Patch embryos

Paige Snider, Olga Simmons, Rhonda Rogers, Rachel Young, Mica Gosnell, Simon Conway

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Although Patch mutants show severe abnormalities in many neural crest-derived structures including the face and the heart, there is a paucity of information characterizing the mechanisms underlying these congenital defects. Via manipulating the genetic background to circumvent early embryonic lethality, our results revealed that Patch phenotypes are most likely due to a significant decrease in migratory neural crest lineage due to diminished neural crest survival and elevated apoptosis. Homozygous mutant neural crest precursors can undergo typical expansion within the neural tube, epithelial-to-mesenchymal transformation, and initiate normal neural crest emigration. Moreover, in vitro explant culture demonstrated that when isolated from the surrounding mesenchyme, Patch mutant neural crest cells (NCCs) can migrate appropriately. Additionally, Patch foregut, notochord and somitic morphogenesis, and Sonic hedgehog expression profiles were all perturbed. Significantly, the timing of lethality and extent of apoptosis correlated with the degree of severity of Patch mutant foregut, notochord, and somite dysfunction. Finally, analysis of Balb/c-enriched surviving Patch mutants revealed that not all the neural crest subpopulations are affected and that Patch mutant neural crest-derived sympathetic ganglia and dorsal root ganglia were unaffected. We hypothesize that loss of normal coordinated signaling from the notochord, foregut, and somites underlies the diminished survival of the neural crest lineage within Patch mutants resulting in subsequent neural crest-deficient phenotypes.

Original languageEnglish
Pages (from-to)551-564
Number of pages14
JournalBirth Defects Research Part A - Clinical and Molecular Teratology
Volume91
Issue number6
DOIs
StatePublished - Jun 2011

Fingerprint

Neural Crest
Embryonic Structures
Apoptosis
Notochord
Somites
Phenotype
Sympathetic Ganglia
Neural Tube
Epithelial-Mesenchymal Transition
Emigration and Immigration
Spinal Ganglia
Mesoderm
Morphogenesis

Keywords

  • Apoptosis
  • Congenital heart defects
  • Genetic background
  • Midface clefting
  • Mouse embryo
  • Neural crest
  • Notochord
  • PDGFα receptor
  • Shh

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Embryology

Cite this

Notochordal and foregut abnormalities correlate with elevated neural crest apoptosis in Patch embryos. / Snider, Paige; Simmons, Olga; Rogers, Rhonda; Young, Rachel; Gosnell, Mica; Conway, Simon.

In: Birth Defects Research Part A - Clinical and Molecular Teratology, Vol. 91, No. 6, 06.2011, p. 551-564.

Research output: Contribution to journalArticle

Snider, Paige ; Simmons, Olga ; Rogers, Rhonda ; Young, Rachel ; Gosnell, Mica ; Conway, Simon. / Notochordal and foregut abnormalities correlate with elevated neural crest apoptosis in Patch embryos. In: Birth Defects Research Part A - Clinical and Molecular Teratology. 2011 ; Vol. 91, No. 6. pp. 551-564.
@article{f46941460df0463cb81028523590e704,
title = "Notochordal and foregut abnormalities correlate with elevated neural crest apoptosis in Patch embryos",
abstract = "Although Patch mutants show severe abnormalities in many neural crest-derived structures including the face and the heart, there is a paucity of information characterizing the mechanisms underlying these congenital defects. Via manipulating the genetic background to circumvent early embryonic lethality, our results revealed that Patch phenotypes are most likely due to a significant decrease in migratory neural crest lineage due to diminished neural crest survival and elevated apoptosis. Homozygous mutant neural crest precursors can undergo typical expansion within the neural tube, epithelial-to-mesenchymal transformation, and initiate normal neural crest emigration. Moreover, in vitro explant culture demonstrated that when isolated from the surrounding mesenchyme, Patch mutant neural crest cells (NCCs) can migrate appropriately. Additionally, Patch foregut, notochord and somitic morphogenesis, and Sonic hedgehog expression profiles were all perturbed. Significantly, the timing of lethality and extent of apoptosis correlated with the degree of severity of Patch mutant foregut, notochord, and somite dysfunction. Finally, analysis of Balb/c-enriched surviving Patch mutants revealed that not all the neural crest subpopulations are affected and that Patch mutant neural crest-derived sympathetic ganglia and dorsal root ganglia were unaffected. We hypothesize that loss of normal coordinated signaling from the notochord, foregut, and somites underlies the diminished survival of the neural crest lineage within Patch mutants resulting in subsequent neural crest-deficient phenotypes.",
keywords = "Apoptosis, Congenital heart defects, Genetic background, Midface clefting, Mouse embryo, Neural crest, Notochord, PDGFα receptor, Shh",
author = "Paige Snider and Olga Simmons and Rhonda Rogers and Rachel Young and Mica Gosnell and Simon Conway",
year = "2011",
month = "6",
doi = "10.1002/bdra.20802",
language = "English",
volume = "91",
pages = "551--564",
journal = "Teratology",
issn = "1542-0752",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Notochordal and foregut abnormalities correlate with elevated neural crest apoptosis in Patch embryos

AU - Snider, Paige

AU - Simmons, Olga

AU - Rogers, Rhonda

AU - Young, Rachel

AU - Gosnell, Mica

AU - Conway, Simon

PY - 2011/6

Y1 - 2011/6

N2 - Although Patch mutants show severe abnormalities in many neural crest-derived structures including the face and the heart, there is a paucity of information characterizing the mechanisms underlying these congenital defects. Via manipulating the genetic background to circumvent early embryonic lethality, our results revealed that Patch phenotypes are most likely due to a significant decrease in migratory neural crest lineage due to diminished neural crest survival and elevated apoptosis. Homozygous mutant neural crest precursors can undergo typical expansion within the neural tube, epithelial-to-mesenchymal transformation, and initiate normal neural crest emigration. Moreover, in vitro explant culture demonstrated that when isolated from the surrounding mesenchyme, Patch mutant neural crest cells (NCCs) can migrate appropriately. Additionally, Patch foregut, notochord and somitic morphogenesis, and Sonic hedgehog expression profiles were all perturbed. Significantly, the timing of lethality and extent of apoptosis correlated with the degree of severity of Patch mutant foregut, notochord, and somite dysfunction. Finally, analysis of Balb/c-enriched surviving Patch mutants revealed that not all the neural crest subpopulations are affected and that Patch mutant neural crest-derived sympathetic ganglia and dorsal root ganglia were unaffected. We hypothesize that loss of normal coordinated signaling from the notochord, foregut, and somites underlies the diminished survival of the neural crest lineage within Patch mutants resulting in subsequent neural crest-deficient phenotypes.

AB - Although Patch mutants show severe abnormalities in many neural crest-derived structures including the face and the heart, there is a paucity of information characterizing the mechanisms underlying these congenital defects. Via manipulating the genetic background to circumvent early embryonic lethality, our results revealed that Patch phenotypes are most likely due to a significant decrease in migratory neural crest lineage due to diminished neural crest survival and elevated apoptosis. Homozygous mutant neural crest precursors can undergo typical expansion within the neural tube, epithelial-to-mesenchymal transformation, and initiate normal neural crest emigration. Moreover, in vitro explant culture demonstrated that when isolated from the surrounding mesenchyme, Patch mutant neural crest cells (NCCs) can migrate appropriately. Additionally, Patch foregut, notochord and somitic morphogenesis, and Sonic hedgehog expression profiles were all perturbed. Significantly, the timing of lethality and extent of apoptosis correlated with the degree of severity of Patch mutant foregut, notochord, and somite dysfunction. Finally, analysis of Balb/c-enriched surviving Patch mutants revealed that not all the neural crest subpopulations are affected and that Patch mutant neural crest-derived sympathetic ganglia and dorsal root ganglia were unaffected. We hypothesize that loss of normal coordinated signaling from the notochord, foregut, and somites underlies the diminished survival of the neural crest lineage within Patch mutants resulting in subsequent neural crest-deficient phenotypes.

KW - Apoptosis

KW - Congenital heart defects

KW - Genetic background

KW - Midface clefting

KW - Mouse embryo

KW - Neural crest

KW - Notochord

KW - PDGFα receptor

KW - Shh

UR - http://www.scopus.com/inward/record.url?scp=79958085533&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958085533&partnerID=8YFLogxK

U2 - 10.1002/bdra.20802

DO - 10.1002/bdra.20802

M3 - Article

VL - 91

SP - 551

EP - 564

JO - Teratology

JF - Teratology

SN - 1542-0752

IS - 6

ER -