Murine arcuate nucleus kisspeptin neurons communicate with GnRH neurons in utero
Standard
Murine arcuate nucleus kisspeptin neurons communicate with GnRH neurons in utero. / Kumar, Devesh ; Freese, Maria ; Drexler, Dagmar ; Hermans-Borgmeyer, Irm; Marquardt, Annette; Boehm, Ulrich.
In: J NEUROSCI, Vol. 34, No. 10, 05.03.2014, p. 3756-66.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Murine arcuate nucleus kisspeptin neurons communicate with GnRH neurons in utero
AU - Kumar, Devesh
AU - Freese, Maria
AU - Drexler, Dagmar
AU - Hermans-Borgmeyer, Irm
AU - Marquardt, Annette
AU - Boehm, Ulrich
PY - 2014/3/5
Y1 - 2014/3/5
N2 - Puberty is a transition period of reproductive development from juvenile stages to adulthood and depends upon the activity of gonadotropin-releasing hormone (GnRH) neurons. GnRH neurons are initially activated in utero but remain quiescent throughout the juvenile period. Premature reactivation of GnRH neurons results in precocious puberty in mice and humans, but the mechanisms underlying developmental control of GnRH neuron activity remain unknown. The neuropeptide kisspeptin, a potent activator of GnRH neurons that is implicated as a critical permissive signal triggering puberty and a major regulator of the adult female hypothalamus-pituitary-gonadal axis, is paradoxically produced by neurons in the developing brain well before puberty onset. Thus, the neural circuits controlling the timing of reproductive maturation remain elusive. Here, we delineate the underlying neural circuitry using conditional genetic transsynaptic tracing in female mouse embryos. We find that kisspeptin-producing neurons in the arcuate nucleus (ARC) already communicate with a specific subset of GnRH neurons in utero. We show that ARC kisspeptin neurons are upstream of GnRH neurons, and that GnRH neuron connectivity to ARC kisspeptin neurons does not depend on their spatial position in the brain. Furthermore, we demonstrate that the neural circuits between ARC kisspeptin and GnRH neurons are fully established and operative before birth. Finally, we find that most GnRH neurons express the kisspeptin receptor GPR54 upon circuit formation, suggesting that the signaling system implicated in gatekeeping puberty becomes operative in the embryo.
AB - Puberty is a transition period of reproductive development from juvenile stages to adulthood and depends upon the activity of gonadotropin-releasing hormone (GnRH) neurons. GnRH neurons are initially activated in utero but remain quiescent throughout the juvenile period. Premature reactivation of GnRH neurons results in precocious puberty in mice and humans, but the mechanisms underlying developmental control of GnRH neuron activity remain unknown. The neuropeptide kisspeptin, a potent activator of GnRH neurons that is implicated as a critical permissive signal triggering puberty and a major regulator of the adult female hypothalamus-pituitary-gonadal axis, is paradoxically produced by neurons in the developing brain well before puberty onset. Thus, the neural circuits controlling the timing of reproductive maturation remain elusive. Here, we delineate the underlying neural circuitry using conditional genetic transsynaptic tracing in female mouse embryos. We find that kisspeptin-producing neurons in the arcuate nucleus (ARC) already communicate with a specific subset of GnRH neurons in utero. We show that ARC kisspeptin neurons are upstream of GnRH neurons, and that GnRH neuron connectivity to ARC kisspeptin neurons does not depend on their spatial position in the brain. Furthermore, we demonstrate that the neural circuits between ARC kisspeptin and GnRH neurons are fully established and operative before birth. Finally, we find that most GnRH neurons express the kisspeptin receptor GPR54 upon circuit formation, suggesting that the signaling system implicated in gatekeeping puberty becomes operative in the embryo.
KW - Animals
KW - Arcuate Nucleus of Hypothalamus
KW - Female
KW - Gonadotropin-Releasing Hormone
KW - Mice
KW - Mice, 129 Strain
KW - Mice, Inbred C57BL
KW - Nerve Net
KW - Neurons
KW - Pregnancy
KW - Receptors, G-Protein-Coupled
U2 - 10.1523/JNEUROSCI.5123-13.2014
DO - 10.1523/JNEUROSCI.5123-13.2014
M3 - SCORING: Journal article
C2 - 24599473
VL - 34
SP - 3756
EP - 3766
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 10
ER -