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The Role of the Atypical Cadherin Fa...

Bagherie-Lachidan, Mazdak.

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The Role of the Atypical Cadherin Fat4 during Early Mouse Kidney Induction and Mesenchymal to Epithelial Transition.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of the Atypical Cadherin Fat4 during Early Mouse Kidney Induction and Mesenchymal to Epithelial Transition./
Author:	Bagherie-Lachidan, Mazdak.
Description:	280 p.
Notes:	Source: Dissertation Abstracts International, Volume: 77-06(E), Section: B.
Contained By:	Dissertation Abstracts International77-06B(E).
Subject:	Biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3746224
ISBN:	9781339394862

The Role of the Atypical Cadherin Fat4 during Early Mouse Kidney Induction and Mesenchymal to Epithelial Transition.
Bagherie-Lachidan, Mazdak.

The Role of the Atypical Cadherin Fat4 during Early Mouse Kidney Induction and Mesenchymal to Epithelial Transition. - 280 p.

Source: Dissertation Abstracts International, Volume: 77-06(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2015.

Mammalian kidney development is a tightly regulated process that requires proper signaling among three different cellular compartments: the ureteric bud (UB; epithelial), the condensing mesenchyme (CM) and the stroma. Improper signaling between these three cell lineages can result in renal hypoplasia and/or dysplasia. Fat4 is an atypical cadherin involved in planar cell polarity (PCP), growth and cell adhesion. It has been proposed that Fat4 might work with another atypical cadherin Dachsous1 (Dchs1) and the Golgi-localized kinase Four-jointed1 (Fjx1). My thesis examined Fat4 and novel genetic interactions with Fat4 during two stages of mouse kidney development: nephron progenitor renewal and early kidney induction. I determined that Fat4-/- single mutants have an expanded renal progenitor pool (i.e. larger CM aggregates) and found that this phenotype is independent of core PCP and Hippo signaling. Loss of Dchs1 also resulted in expansion of the CM. Tissue-specific deletions show that Fat4 acts non-autonomously in the renal stroma to regulate the nephron progenitor pool. Gene expression analyses demonstrated that BMP, Notch and FGF signaling are altered in Fat4 mutants. I also found that Fat4-/-;Fjx1-/- double mutants exhibit duplex kidneys. Since increased GDNF-RET signaling also leads to duplex kidneys, I reduced GDNF signaling by examining GDNF+/-;Fat4-/-;Fjx1-/- triple mutants. Importantly, these mice did not exhibit duplex kidneys, suggesting that Fat4 and Fjx1 suppress excessive levels of GDNF-RET signaling. Overall, my thesis supports a model whereby 1) Fat4 in the stroma binds to Dchs1 in the CM to restrict renal progenitor self-renewal and, 2) Fat4 and Fjx1 restrict GDNF-RET signaling during kidney induction and subsequent branching.

ISBN: 9781339394862Subjects--Topical Terms:

522710
Biology.

The Role of the Atypical Cadherin Fat4 during Early Mouse Kidney Induction and Mesenchymal to Epithelial Transition.
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020 $a 9781339394862
035 $a (MiAaPQ)AAI3746224
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100 1 $a Bagherie-Lachidan, Mazdak. $3 3193226
245 1 4 $a The Role of the Atypical Cadherin Fat4 during Early Mouse Kidney Induction and Mesenchymal to Epithelial Transition.
300 $a 280 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-06(E), Section: B.
500 $a Adviser: Helen McNeill.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2015.
520 $a Mammalian kidney development is a tightly regulated process that requires proper signaling among three different cellular compartments: the ureteric bud (UB; epithelial), the condensing mesenchyme (CM) and the stroma. Improper signaling between these three cell lineages can result in renal hypoplasia and/or dysplasia. Fat4 is an atypical cadherin involved in planar cell polarity (PCP), growth and cell adhesion. It has been proposed that Fat4 might work with another atypical cadherin Dachsous1 (Dchs1) and the Golgi-localized kinase Four-jointed1 (Fjx1). My thesis examined Fat4 and novel genetic interactions with Fat4 during two stages of mouse kidney development: nephron progenitor renewal and early kidney induction. I determined that Fat4-/- single mutants have an expanded renal progenitor pool (i.e. larger CM aggregates) and found that this phenotype is independent of core PCP and Hippo signaling. Loss of Dchs1 also resulted in expansion of the CM. Tissue-specific deletions show that Fat4 acts non-autonomously in the renal stroma to regulate the nephron progenitor pool. Gene expression analyses demonstrated that BMP, Notch and FGF signaling are altered in Fat4 mutants. I also found that Fat4-/-;Fjx1-/- double mutants exhibit duplex kidneys. Since increased GDNF-RET signaling also leads to duplex kidneys, I reduced GDNF signaling by examining GDNF+/-;Fat4-/-;Fjx1-/- triple mutants. Importantly, these mice did not exhibit duplex kidneys, suggesting that Fat4 and Fjx1 suppress excessive levels of GDNF-RET signaling. Overall, my thesis supports a model whereby 1) Fat4 in the stroma binds to Dchs1 in the CM to restrict renal progenitor self-renewal and, 2) Fat4 and Fjx1 restrict GDNF-RET signaling during kidney induction and subsequent branching.
590 $a School code: 0779.
650 4 $a Biology. $3 522710
650 4 $a Developmental biology. $3 592588
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710 2 $a University of Toronto (Canada). $b Molecular and Medical Genetics. $3 3177543
773 0 $t Dissertation Abstracts International $g 77-06B(E).
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791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3746224