Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts

Pascale L. Durbec, Lena B. Larsson-Blomberg, Anita Schuchardt, Frank Costantini, Vassilis Pachnis

Research output: Contribution to journalArticle

335 Citations (Scopus)

Abstract

c-ret encodes a tyrosine kinase receptor that is necessary for normal development of the mammalian enteric nervous system. Germline mutations in c-ret lead to congenital megacolon in humans, while a loss-of-function allele (ret.k-) causes intestinal aganglionosis in mice. Here we examine in detail the function of c-ret during neurogenesis, as well as the lineage relationships among cell populations in the enteric nervous system and the sympathetic nervous system that are dependent on c-ret function. We report that, while the intestine of newborn ret.k- mice is devoid of enteric ganglia, the esophagus and stomach are only partially affected; furthermore, the superior cervical ganglion is absent, while more posterior sympathetic ganglia and the adrenal medulla are unaffected. Analysis of mutant embryos shows that the superior cervical ganglion anlage is present at E10.5, but absent by E12.5, suggesting that c-ret is required for the survival or proliferation of sympathetic neuroblasts. In situ hybridization studies, as well as direct labelling of cells with DiI, indicate that a common pool of neural crest cells derived from the postotic hindbrain normally gives rise to most of the enteric nervous system and the superior cervical ganglion, and is uniquely dependent on c-ret function for normal development. We term this the sympathoenteric lineage. In contrast, a distinct sympathoadrenal lineage derived from trunk neural crest forms the more posterior sympathetic ganglia, and also contributes to the foregut enteric nervous system. Overall, our studies reveal previously unknown complexities of cell lineage and genetic control mechanisms in the developing mammalian peripheral nervous system.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalDevelopment
Volume122
Issue number1
StatePublished - Jan 1 1996

Fingerprint

Enteric Nervous System
nervous system
Superior Cervical Ganglion
Sympathetic Ganglia
Neural Crest
Hirschsprung Disease
Rhombencephalon
Adrenal Medulla
Germ-Line Mutation
Sympathetic Nervous System
Neurogenesis
Peripheral Nervous System
Receptor Protein-Tyrosine Kinases
Cell Lineage
loss of function
Ganglia
Esophagus
Intestines
In Situ Hybridization
Stomach

Keywords

  • Enteric nervous system
  • Receptor tyrosine kinase
  • Superior cervical ganglion
  • c-ret

Cite this

Durbec, P. L., Larsson-Blomberg, L. B., Schuchardt, A., Costantini, F., & Pachnis, V. (1996). Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts. Development, 122(1), 349-358.

Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts. / Durbec, Pascale L.; Larsson-Blomberg, Lena B.; Schuchardt, Anita; Costantini, Frank; Pachnis, Vassilis.

In: Development, Vol. 122, No. 1, 01.01.1996, p. 349-358.

Research output: Contribution to journalArticle

Durbec, PL, Larsson-Blomberg, LB, Schuchardt, A, Costantini, F & Pachnis, V 1996, 'Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts', Development, vol. 122, no. 1, pp. 349-358.
Durbec PL, Larsson-Blomberg LB, Schuchardt A, Costantini F, Pachnis V. Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts. Development. 1996 Jan 1;122(1):349-358.
Durbec, Pascale L. ; Larsson-Blomberg, Lena B. ; Schuchardt, Anita ; Costantini, Frank ; Pachnis, Vassilis. / Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts. In: Development. 1996 ; Vol. 122, No. 1. pp. 349-358.
@article{8069faa87e20417d9485d058d69a9b2e,
title = "Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts",
abstract = "c-ret encodes a tyrosine kinase receptor that is necessary for normal development of the mammalian enteric nervous system. Germline mutations in c-ret lead to congenital megacolon in humans, while a loss-of-function allele (ret.k-) causes intestinal aganglionosis in mice. Here we examine in detail the function of c-ret during neurogenesis, as well as the lineage relationships among cell populations in the enteric nervous system and the sympathetic nervous system that are dependent on c-ret function. We report that, while the intestine of newborn ret.k- mice is devoid of enteric ganglia, the esophagus and stomach are only partially affected; furthermore, the superior cervical ganglion is absent, while more posterior sympathetic ganglia and the adrenal medulla are unaffected. Analysis of mutant embryos shows that the superior cervical ganglion anlage is present at E10.5, but absent by E12.5, suggesting that c-ret is required for the survival or proliferation of sympathetic neuroblasts. In situ hybridization studies, as well as direct labelling of cells with DiI, indicate that a common pool of neural crest cells derived from the postotic hindbrain normally gives rise to most of the enteric nervous system and the superior cervical ganglion, and is uniquely dependent on c-ret function for normal development. We term this the sympathoenteric lineage. In contrast, a distinct sympathoadrenal lineage derived from trunk neural crest forms the more posterior sympathetic ganglia, and also contributes to the foregut enteric nervous system. Overall, our studies reveal previously unknown complexities of cell lineage and genetic control mechanisms in the developing mammalian peripheral nervous system.",
keywords = "Enteric nervous system, Receptor tyrosine kinase, Superior cervical ganglion, c-ret",
author = "Durbec, {Pascale L.} and Larsson-Blomberg, {Lena B.} and Anita Schuchardt and Frank Costantini and Vassilis Pachnis",
year = "1996",
month = "1",
day = "1",
language = "English (US)",
volume = "122",
pages = "349--358",
journal = "Development",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "1",

}

TY - JOUR

T1 - Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts

AU - Durbec, Pascale L.

AU - Larsson-Blomberg, Lena B.

AU - Schuchardt, Anita

AU - Costantini, Frank

AU - Pachnis, Vassilis

PY - 1996/1/1

Y1 - 1996/1/1

N2 - c-ret encodes a tyrosine kinase receptor that is necessary for normal development of the mammalian enteric nervous system. Germline mutations in c-ret lead to congenital megacolon in humans, while a loss-of-function allele (ret.k-) causes intestinal aganglionosis in mice. Here we examine in detail the function of c-ret during neurogenesis, as well as the lineage relationships among cell populations in the enteric nervous system and the sympathetic nervous system that are dependent on c-ret function. We report that, while the intestine of newborn ret.k- mice is devoid of enteric ganglia, the esophagus and stomach are only partially affected; furthermore, the superior cervical ganglion is absent, while more posterior sympathetic ganglia and the adrenal medulla are unaffected. Analysis of mutant embryos shows that the superior cervical ganglion anlage is present at E10.5, but absent by E12.5, suggesting that c-ret is required for the survival or proliferation of sympathetic neuroblasts. In situ hybridization studies, as well as direct labelling of cells with DiI, indicate that a common pool of neural crest cells derived from the postotic hindbrain normally gives rise to most of the enteric nervous system and the superior cervical ganglion, and is uniquely dependent on c-ret function for normal development. We term this the sympathoenteric lineage. In contrast, a distinct sympathoadrenal lineage derived from trunk neural crest forms the more posterior sympathetic ganglia, and also contributes to the foregut enteric nervous system. Overall, our studies reveal previously unknown complexities of cell lineage and genetic control mechanisms in the developing mammalian peripheral nervous system.

AB - c-ret encodes a tyrosine kinase receptor that is necessary for normal development of the mammalian enteric nervous system. Germline mutations in c-ret lead to congenital megacolon in humans, while a loss-of-function allele (ret.k-) causes intestinal aganglionosis in mice. Here we examine in detail the function of c-ret during neurogenesis, as well as the lineage relationships among cell populations in the enteric nervous system and the sympathetic nervous system that are dependent on c-ret function. We report that, while the intestine of newborn ret.k- mice is devoid of enteric ganglia, the esophagus and stomach are only partially affected; furthermore, the superior cervical ganglion is absent, while more posterior sympathetic ganglia and the adrenal medulla are unaffected. Analysis of mutant embryos shows that the superior cervical ganglion anlage is present at E10.5, but absent by E12.5, suggesting that c-ret is required for the survival or proliferation of sympathetic neuroblasts. In situ hybridization studies, as well as direct labelling of cells with DiI, indicate that a common pool of neural crest cells derived from the postotic hindbrain normally gives rise to most of the enteric nervous system and the superior cervical ganglion, and is uniquely dependent on c-ret function for normal development. We term this the sympathoenteric lineage. In contrast, a distinct sympathoadrenal lineage derived from trunk neural crest forms the more posterior sympathetic ganglia, and also contributes to the foregut enteric nervous system. Overall, our studies reveal previously unknown complexities of cell lineage and genetic control mechanisms in the developing mammalian peripheral nervous system.

KW - Enteric nervous system

KW - Receptor tyrosine kinase

KW - Superior cervical ganglion

KW - c-ret

UR - http://www.scopus.com/inward/record.url?scp=0030065375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030065375&partnerID=8YFLogxK

M3 - Article

C2 - 8565847

AN - SCOPUS:0030065375

VL - 122

SP - 349

EP - 358

JO - Development

JF - Development

SN - 0950-1991

IS - 1

ER -