Professional Documents
Culture Documents
Lamprey Reproduction: Understanding
Lamprey Reproduction: Understanding
Can you summarise the focus and objectives of novel interventive GnRH analogs as
of your research? for better medical therapies such,
or for use in controlling the
The major goal of my current research has been
reproduction in fish mapping
to test the global hypothesis that lamprey have
aquaculture. A of the lamprey
a hypothalamic-pituitary-gonadal axis. The
new method of genome started
specific objectives of our GnRH receptor work
sterilisation in Jan 2005 (www.
are to characterise:
would also genome.gov/12511858). Nine
• Lamprey GnRHR-2 and 3 sequences and be very non-mammalian organisms were chosen
perform phylogenetic analysis to determine useful in by the NIH for mapping the genome, each of
function in second messenger activation assays the field which represents a position on the evolutionary
and ligand-binding specificity of sea timeline marked by important changes in
lamprey animal anatomy, physiology, development
• Key functional features of lamprey GnRH
control or behaviour. It is estimated that the current
receptor-1, 2 or 3 (type-II receptors) by site-
in the coverage of the genome is about 5.9X, which
directed mutagenic studies
Great infers that much of the genome has been
• Differential signalling properties and the Lakes. sequenced and available for analysis using
mechanisms of the termination of the
In what
intracellular signalling attributable to the
ways have
C-terminal tail of lamprey GnRH receptor-1, 2
your laboratory
or 3 by using transient cell lines that express
and collaborators
either full-length or point mutants
been a major force in
What, specifically, do you anticipate will be demonstrating the value of the sea
the key outcomes of your research? lamprey as a model system for evolutionary
the trace archives and the partially assembled
analyses? Indeed, can you expand on why
Identification and functional studies of novel genome by Ensembl.
the sea lamprey is considered a viable and
GnRH receptors from basal vertebrates can
useful model? Findings from your laboratory have
provide valuable information on the complexity
illustrated that the acquisition of the
and molecular delineation of the interactions As an agnathan, the oldest extant lineage of
hypothalamus was a seminal event in
of GnRHs and their respective receptors, and vertebrates, the sea lamprey has become a
vertebrate evolution. To what extent – and in
provide considerable insight and clarification model system for analysis of the evolution
what sense – do these findings constitute a
into the molecular basis for transmission of of many genes and systems including the
major breakthrough in research?
the signal to the G protein or other signalling evolution of the neuroendocrine regulation of
pathways. Understanding the comparative reproduction and the evolution of development Our existing data suggest the existence
aspects of the structural elements of GnRHs (EvoDev). Lampreys as basal vertebrates were of a primitive, overlapping yet functional
and their receptors can lead to the development identified to be integral to evolutionary studies; hypothalamic-pituitary-gonadal (HPG)
64 INTERNATIONAL INNOVATION
DR STACIA SOWER
WWW.RESEARCHMEDIA.EU 65
INTELLIGENCE several neuroendocrine and environmental factors. processes. Coupled with this, Sower’s group has
Drawing on this, Sower comments: “In order to identified GnRH receptors in lamprey which
INSIGHT FROM LAMPREY GENOME:
control fish puberty or sterilise fish, we need to share several characteristics seen in type-I and
STRUCTURE-FUNCTION STUDIES OF
NOVEL GNRH RECEPTORS understand the underlying mechanisms that trigger type-II vertebrate GnRH receptors. Highlighting
and control puberty”. She continues: “The ongoing the significance of these findings, Sower states:
OBJECTIVES research in my laboratory is to further identify key “The high conservation of GnRH and its receptor
The laboratory’s ongoing studies focus on reproductive hypothalamic and pituitary hormones throughout vertebrate species makes the lamprey
the molecular, biochemical and functional in lamprey and to determine interrelationships of model highly appropriate for examining the GnRH
studies to test the overall hypothesis these hormones under specific reproductive stages system in terms of its ligands and novel receptors”.
that lamprey GnRHs, GTH and their and environmental conditions”. Sower’s team of Furthermore, the team has recently located a novel
receptor(s) share common functional and dedicated researchers anticipate their programme GnRH (called 1GnRH-II) and two novel GnRH
developmental features compared to later will provide key findings which will contribute to the receptors (lGnRHR-2 and 3). This discovery has
evolved vertebrates. The research embraces development of better medical therapies and novel provided a unique opportunity for comparative
new methodologies that are becoming strategies for controlling reproduction in fish. and evolutionary analysis of the neuroendocrine
available through the disciplines of hormonal system in vertebrates.
REARING ITS ANCIENT HEAD
genomics, proteomics and bioinformatics.
In focusing upon lampreys – that is, the oldest Within this evolutionary context, Sower and her
KEY COLLABORATORS extant species on Earth – Sower’s research bears collaborators have formulated a new hypothesis
Professor Hiroshi Kawauchi, Kitsato enormous relevance in determining neuroendocrine relating to the neuroendocrine control of
University, Japan development in evolutionary terms. Indeed, reproduction in lamprey. The team proposes
Professor Masumi Nozaki, Niigata landmark findings that have recently emerged from that the neuroendocrine and thyroid functions
University, Japan Sower’s laboratory illustrate that the acquisition of in the agnathan sea lamprey are simpler than
the hypothalamus in lamprey was a paradigmatic those exhibited in later vertebrates. This is
KEY FORMER GRADUATE STUDENTS
development in vertebrate evolution. She observes: based upon the formulation that in lamprey,
Dr Matthew Silver, Cell Signaling “The hypothalamic-pituitary (HP) system is one glycoprotein putatively interacts with two
Technology, MA considered to be a vertebrate innovation and receptors. “In our research, this transforming
Dr Scott Kavanaugh, University of Colorado, seminal event that emerged prior to – or during – the paradigm serves as a model for analysis of the
Boulder differentiation of the ancestral agnathans [jawless evolutionary mechanisms leading to emergence
Dr Mihael Freamat, Boston University, MA fish]”. Despite the highly diverse life cycles and of the highly specialised Gnathostome endocrine
FUNDING reproductive strategies and behaviourial patterns axes,” Sower affirms.
NIH-NCRR of vertebrate fish species, the endocrine system
ROLE OF GENOMICS
NSF observed by Sower and her team is, somewhat
incredibly, conserved throughout gnathostome As a marker of how much our understanding of the
NH-AES
(species bearing mouths and jaws) lineages. neuroendocrine system in lamprey has advanced,
CONTACT Sower recalls the paucity of knowledge that had
Stacia A Sower, PhD Professor FINDINGS AND NEW HYPOTHESES been gleaned when she first entered the field:
Director of Center for Molecular and Sower’s team has adopted a multidisciplinary “When I started my studies 30 years ago, most
Comparative Endocrinology, Biochemistry approach to investigate the structure and function scientists did not think that the lamprey had the
and Molecular Biology Program, Department of GnRHs in lamprey. By assimilating biochemical, same neuroendocrine system as all other jawed
of Molecular, Cellular and Biomedical molecular, immunocytochemical and functional vertebrates. This was an animal with a backbone that
Sciences studies, the team has determined that the lamprey we did not know anything about”. Today, however,
possesses a hypothalamic-pituitary-gonadal studies in this area are enhanced enormously by the
46 College Road axis and that there is a high conservation of the mapping of the lamprey genome. Indeed, the advent
University of New Hampshire mechanisms of GnRH action. However, while of genomics has proven critical in the identification
Durham, NH 03824-3544, USA Gnathostomes are generally seen to have two of ligands, receptors, transcription factors and
T +1 603 862-2103 GnRHs that act as hypothalamic hormones, signalling pathways. Although the lamprey genome
E sasower@cisunix.unh.edu lampreys are the earliest evolved vertebrates for has not, as yet, been fully annotated, efforts are well
which there are demonstrated functional roles underway, with Professor Weiming Li of Michigan
www.unh.edu/biochemistry/sower/index. for three GnRHs that act via the hypothalamic- State University leading a battery of international
html pituitary-gonadal axis controlling reproductive scientists in this pivotal endeavour.
66 INTERNATIONAL INNOVATION