Abstract
The elucidation of the genomes of a large number of mammalian species has produced a huge amount of data on which to base physiological studies. These endeavours have also produced surprises, not least of which has been the revelation that the number of protein coding genes needed to make a mammal is only 22333 (give or take). However, this small number belies an unanticipated complexity that has only recently been revealed as a result of genomic studies. This complexity is evident at a number of levels: (i) cis-regulatory sequences; (ii) noncoding and antisense mRNAs, most of which have no known function; (iii) alternative splicing that results in the generation of multiple, subtly different mature mRNAs from the precursor transcript encoded by a single gene; and (iv) post-translational processing and modification. In this review, we examine the steps being taken to decipher genome complexity in the context of gene expression, regulation and function in the hypothalamic-neurohypophyseal system (HNS). Five unique stories explain: (i) the use of transcriptomics to identify genes involved in the response to physiological (dehydration) and pathological (hypertension) cues; (ii) the use of mass spectrometry for single-cell level identification of biological active peptides in the HNS, and to measure in vitro release; (iii) the use of transgenic lines that express fusion transgenes enabling (by cross-breeding) the generation of double transgenic lines that can be used to study vasopressin (AVP) and oxytocin (OXT) neurones in the HNS, as well as their neuroanatomy, electrophysiology and activation upon exposure to any given stimulus; (iv) the use of viral vectors to demonstrate that somato-dendritically released AVP plays an important role in cardiovascular homeostasis by binding to V1a receptors on local somata and dendrites; and (v) the use of virally-mediated optogenetics to dissect the role of OXT and AVP in the modulation of a wide variety of behaviours.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 539-553 |
| Number of pages | 15 |
| Journal | Journal of Neuroendocrinology |
| Volume | 24 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2012 |
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Keywords
- Genome
- Hypothalamic-neurohypophyseal system
- Neuropeptidome
- Oxytocin
- Proteome
- Transcriptome
- Transgenic rats
- Vasopressin
- Viral vectors
ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism
- Endocrine and Autonomic Systems
- Cellular and Molecular Neuroscience
Cite this
The Hypothalamic-Neurohypophyseal System : From Genome to Physiology. / Murphy, D.; Konopacka, A.; Hindmarch, C.; Paton, J. F.R.; Sweedler, J. V.; Gillette, M. U.; Ueta, Y.; Grinevich, V.; Lozic, M.; Japundzic-Zigon, N.
In: Journal of Neuroendocrinology, Vol. 24, No. 4, 01.04.2012, p. 539-553.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - The Hypothalamic-Neurohypophyseal System
T2 - From Genome to Physiology
AU - Murphy, D.
AU - Konopacka, A.
AU - Hindmarch, C.
AU - Paton, J. F.R.
AU - Sweedler, J. V.
AU - Gillette, M. U.
AU - Ueta, Y.
AU - Grinevich, V.
AU - Lozic, M.
AU - Japundzic-Zigon, N.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - The elucidation of the genomes of a large number of mammalian species has produced a huge amount of data on which to base physiological studies. These endeavours have also produced surprises, not least of which has been the revelation that the number of protein coding genes needed to make a mammal is only 22333 (give or take). However, this small number belies an unanticipated complexity that has only recently been revealed as a result of genomic studies. This complexity is evident at a number of levels: (i) cis-regulatory sequences; (ii) noncoding and antisense mRNAs, most of which have no known function; (iii) alternative splicing that results in the generation of multiple, subtly different mature mRNAs from the precursor transcript encoded by a single gene; and (iv) post-translational processing and modification. In this review, we examine the steps being taken to decipher genome complexity in the context of gene expression, regulation and function in the hypothalamic-neurohypophyseal system (HNS). Five unique stories explain: (i) the use of transcriptomics to identify genes involved in the response to physiological (dehydration) and pathological (hypertension) cues; (ii) the use of mass spectrometry for single-cell level identification of biological active peptides in the HNS, and to measure in vitro release; (iii) the use of transgenic lines that express fusion transgenes enabling (by cross-breeding) the generation of double transgenic lines that can be used to study vasopressin (AVP) and oxytocin (OXT) neurones in the HNS, as well as their neuroanatomy, electrophysiology and activation upon exposure to any given stimulus; (iv) the use of viral vectors to demonstrate that somato-dendritically released AVP plays an important role in cardiovascular homeostasis by binding to V1a receptors on local somata and dendrites; and (v) the use of virally-mediated optogenetics to dissect the role of OXT and AVP in the modulation of a wide variety of behaviours.
AB - The elucidation of the genomes of a large number of mammalian species has produced a huge amount of data on which to base physiological studies. These endeavours have also produced surprises, not least of which has been the revelation that the number of protein coding genes needed to make a mammal is only 22333 (give or take). However, this small number belies an unanticipated complexity that has only recently been revealed as a result of genomic studies. This complexity is evident at a number of levels: (i) cis-regulatory sequences; (ii) noncoding and antisense mRNAs, most of which have no known function; (iii) alternative splicing that results in the generation of multiple, subtly different mature mRNAs from the precursor transcript encoded by a single gene; and (iv) post-translational processing and modification. In this review, we examine the steps being taken to decipher genome complexity in the context of gene expression, regulation and function in the hypothalamic-neurohypophyseal system (HNS). Five unique stories explain: (i) the use of transcriptomics to identify genes involved in the response to physiological (dehydration) and pathological (hypertension) cues; (ii) the use of mass spectrometry for single-cell level identification of biological active peptides in the HNS, and to measure in vitro release; (iii) the use of transgenic lines that express fusion transgenes enabling (by cross-breeding) the generation of double transgenic lines that can be used to study vasopressin (AVP) and oxytocin (OXT) neurones in the HNS, as well as their neuroanatomy, electrophysiology and activation upon exposure to any given stimulus; (iv) the use of viral vectors to demonstrate that somato-dendritically released AVP plays an important role in cardiovascular homeostasis by binding to V1a receptors on local somata and dendrites; and (v) the use of virally-mediated optogenetics to dissect the role of OXT and AVP in the modulation of a wide variety of behaviours.
KW - Genome
KW - Hypothalamic-neurohypophyseal system
KW - Neuropeptidome
KW - Oxytocin
KW - Proteome
KW - Transcriptome
KW - Transgenic rats
KW - Vasopressin
KW - Viral vectors
UR - http://www.scopus.com/inward/record.url?scp=84858832918&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858832918&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2826.2011.02241.x
DO - 10.1111/j.1365-2826.2011.02241.x
M3 - Review article
C2 - 22448850
AN - SCOPUS:84858832918
VL - 24
SP - 539
EP - 553
JO - Journal of Neuroendocrinology
JF - Journal of Neuroendocrinology
SN - 0953-8194
IS - 4
ER -