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The Role of Orthopedia (OTP) in the ...

Wircer, Einav,

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The Role of Orthopedia (OTP) in the Development and Function of Oxytocinergic Neurons /

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of Orthopedia (OTP) in the Development and Function of Oxytocinergic Neurons // Einav Wircer.
Author:	Wircer, Einav,
Description:	1 electronic resource (73 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 82-09, Section: B.
Contained By:	Dissertations Abstracts International82-09B.
Subject:	Aquatic sciences. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28465299
ISBN:	9798597000664

The Role of Orthopedia (OTP) in the Development and Function of Oxytocinergic Neurons /
Wircer, Einav,

The Role of Orthopedia (OTP) in the Development and Function of Oxytocinergic Neurons /Einav Wircer. - 1 electronic resource (73 pages)

Source: Dissertations Abstracts International, Volume: 82-09, Section: B.

Disruptions of the oxytocin (OXT) system in humans have been implicated in many pathological conditions, including Prader-Willi syndrome and autism. Yet, very little is known of how hypothalamic OXT-ergic neurons exert their function. Moreover, OXT-expressing neurons are highly heterogeneous in morphology and function and are defined and identified mainly by the existence of their major neuropeptide. A major factor involved in the development of OXT neurons is orthopedia (Otp). In mice there is a single otp gene and the null pups die at birth. This early lethality hinders the investigation of possible functions of this protein in OXT cells at later stages. In the zebrafish, there are two Otp paralogs - otpa and otpb, which have partial redundancy in their activity. Fish carrying mutation in either one of the otp genes are viable and fertile. In the absence of both genes fish do not develop OXT neurons as well as other types of neurosecretory cells and die at an embryonic stage, similar to the mouse knockout. Therefore, zebrafish presents us with a unique opportunity to examine sub-functions of Otp in a live animal. In this PhD thesis I used the zebrafish model and examined aspects in Otp's function in the regulation of OXT cells development and the modulation of fish behavior. According to my findings mutation in otpa led to an upregulation in OXT expression in the fish posterior tuberculum (PT) in a previously un-recognized group of cells. These specific PT neurons were also found to co-localize with an EGFP reporter in the Tg(oxt:egfp) line, which express EGFP genetic marker under 650bp OXT regulatory element. Yet, in wild type transgenic fish the EGFP cells in the PT exist, though normally do not express detectable levels of OXT, and this neuropeptide is detected specifically in cells in preoptic region (NPO). I have characterized some of the molecular and anatomical features of this newly identified OXT-ergic cluster in the PT and found that this small group of cells, readily detectable in the Tg(oxt:egfp) fish, under basal conditions express very low levels of OXT in wild type fish. In addition, these cells were found to express OXT receptor. By examining the projections of these neuronal cells, I found that the majority of the PT OXT-ergic neurons project to the hindbrain and spinal cord.In addition to the up regulation in OXT expression, defects in otpa led to marked changes in the fish's behavioral response to an Open field test. Otpa mutants were also found to have defects intheir social interactions, as they spent less time shoaling than wild types. Interestingly, by specifically ablating posterior OXT-ergic neurons in Tg(oxt:egfp) with a wild type genetic background I was able to induce changes in the fish's social behavior without changing their response to an open field. This may indicate of the specific mode by which the developmental factor Otpa can regulate complex adult behavior by affecting the development of specific cell types.

English

ISBN: 9798597000664Subjects--Topical Terms:

3174300
Aquatic sciences.
Subjects--Index Terms:

Oxytocin (OXT) system

The Role of Orthopedia (OTP) in the Development and Function of Oxytocinergic Neurons /
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520 $a Disruptions of the oxytocin (OXT) system in humans have been implicated in many pathological conditions, including Prader-Willi syndrome and autism. Yet, very little is known of how hypothalamic OXT-ergic neurons exert their function. Moreover, OXT-expressing neurons are highly heterogeneous in morphology and function and are defined and identified mainly by the existence of their major neuropeptide. A major factor involved in the development of OXT neurons is orthopedia (Otp). In mice there is a single otp gene and the null pups die at birth. This early lethality hinders the investigation of possible functions of this protein in OXT cells at later stages. In the zebrafish, there are two Otp paralogs - otpa and otpb, which have partial redundancy in their activity. Fish carrying mutation in either one of the otp genes are viable and fertile. In the absence of both genes fish do not develop OXT neurons as well as other types of neurosecretory cells and die at an embryonic stage, similar to the mouse knockout. Therefore, zebrafish presents us with a unique opportunity to examine sub-functions of Otp in a live animal. In this PhD thesis I used the zebrafish model and examined aspects in Otp's function in the regulation of OXT cells development and the modulation of fish behavior. According to my findings mutation in otpa led to an upregulation in OXT expression in the fish posterior tuberculum (PT) in a previously un-recognized group of cells. These specific PT neurons were also found to co-localize with an EGFP reporter in the Tg(oxt:egfp) line, which express EGFP genetic marker under 650bp OXT regulatory element. Yet, in wild type transgenic fish the EGFP cells in the PT exist, though normally do not express detectable levels of OXT, and this neuropeptide is detected specifically in cells in preoptic region (NPO). I have characterized some of the molecular and anatomical features of this newly identified OXT-ergic cluster in the PT and found that this small group of cells, readily detectable in the Tg(oxt:egfp) fish, under basal conditions express very low levels of OXT in wild type fish. In addition, these cells were found to express OXT receptor. By examining the projections of these neuronal cells, I found that the majority of the PT OXT-ergic neurons project to the hindbrain and spinal cord.In addition to the up regulation in OXT expression, defects in otpa led to marked changes in the fish's behavioral response to an Open field test. Otpa mutants were also found to have defects intheir social interactions, as they spent less time shoaling than wild types. Interestingly, by specifically ablating posterior OXT-ergic neurons in Tg(oxt:egfp) with a wild type genetic background I was able to induce changes in the fish's social behavior without changing their response to an open field. This may indicate of the specific mode by which the developmental factor Otpa can regulate complex adult behavior by affecting the development of specific cell types.
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653 $a Autism
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653 $a Proteins
653 $a Neurosecretory cells
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