#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Actin Depolymerizing Factors Cofilin1 and Destrin Are Required for Ureteric Bud Branching Morphogenesis


The actin depolymerizing factors (ADFs) play important roles in several cellular processes that require cytoskeletal rearrangements, such as cell migration, but little is known about the in vivo functions of ADFs in developmental events like branching morphogenesis. While the molecular control of ureteric bud (UB) branching during kidney development has been extensively studied, the detailed cellular events underlying this process remain poorly understood. To gain insight into the role of actin cytoskeletal dynamics during renal branching morphogenesis, we studied the functional requirements for the closely related ADFs cofilin1 (Cfl1) and destrin (Dstn) during mouse development. Either deletion of Cfl1 in UB epithelium or an inactivating mutation in Dstn has no effect on renal morphogenesis, but simultaneous lack of both genes arrests branching morphogenesis at an early stage, revealing considerable functional overlap between cofilin1 and destrin. Lack of Cfl1 and Dstn in the UB causes accumulation of filamentous actin, disruption of normal epithelial organization, and defects in cell migration. Animals with less severe combinations of mutant Cfl1 and Dstn alleles, which retain one wild-type Cfl1 or Dstn allele, display abnormalities including ureter duplication, renal hypoplasia, and abnormal kidney shape. The results indicate that ADF activity, provided by either cofilin1 or destrin, is essential in UB epithelial cells for normal growth and branching.


Vyšlo v časopise: Actin Depolymerizing Factors Cofilin1 and Destrin Are Required for Ureteric Bud Branching Morphogenesis. PLoS Genet 6(10): e32767. doi:10.1371/journal.pgen.1001176
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001176

Souhrn

The actin depolymerizing factors (ADFs) play important roles in several cellular processes that require cytoskeletal rearrangements, such as cell migration, but little is known about the in vivo functions of ADFs in developmental events like branching morphogenesis. While the molecular control of ureteric bud (UB) branching during kidney development has been extensively studied, the detailed cellular events underlying this process remain poorly understood. To gain insight into the role of actin cytoskeletal dynamics during renal branching morphogenesis, we studied the functional requirements for the closely related ADFs cofilin1 (Cfl1) and destrin (Dstn) during mouse development. Either deletion of Cfl1 in UB epithelium or an inactivating mutation in Dstn has no effect on renal morphogenesis, but simultaneous lack of both genes arrests branching morphogenesis at an early stage, revealing considerable functional overlap between cofilin1 and destrin. Lack of Cfl1 and Dstn in the UB causes accumulation of filamentous actin, disruption of normal epithelial organization, and defects in cell migration. Animals with less severe combinations of mutant Cfl1 and Dstn alleles, which retain one wild-type Cfl1 or Dstn allele, display abnormalities including ureter duplication, renal hypoplasia, and abnormal kidney shape. The results indicate that ADF activity, provided by either cofilin1 or destrin, is essential in UB epithelial cells for normal growth and branching.


Zdroje

1. Van TroysM

HuyckL

LeymanS

DhaeseS

VandekerkhoveJ

2008 Ins and outs of ADF/cofilin activity and regulation. Eur J Cell Biol 87 649 667

2. InsallRH

MacheskyLM

2009 Actin dynamics at the leading edge: from simple machinery to complex networks. Dev Cell 17 310 322

3. LenartP

BacherCP

DaigleN

HandAR

EilsR

2005 A contractile nuclear actin network drives chromosome congression in oocytes. Nature 436 812 818

4. GurniakCB

PerlasE

WitkeW

2005 The actin depolymerizing factor n-cofilin is essential for neural tube morphogenesis and neural crest cell migration. Dev Biol 278 231 241

5. BellenchiGC

GurniakCB

PerlasE

MiddeiS

Ammassari-TeuleM

2007 N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex. Genes Dev 21 2347 2357

6. IkedaS

CunninghamLA

BoggessD

HawesN

HobsonCD

2003 Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Hum Mol Genet 12 1029 1037

7. DresslerGR

2006 The cellular basis of kidney development. Annu Rev Cell Dev Biol 22 509 529

8. SchedlA

2007 Renal abnormalities and their developmental origin. Nat Rev Genet 8 791 802

9. SaxenL

1987 Organogenesis of the Kidney. Cambridge Cambridge University Press

10. ChiX

MichosO

ShakyaR

RiccioP

EnomotoH

2009 Ret-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis. Dev Cell 17 199 209

11. MichaelL

DaviesJA

2004 Pattern and regulation of cell proliferation during murine ureteric bud development. J Anat 204 241 255

12. MichaelL

SweeneyDE

DaviesJA

2005 A role for microfilament-based contraction in branching morphogenesis of the ureteric bud. Kidney Int 68 2010 2018

13. MeyerTN

SchwesingerC

SampognaRV

VaughnDA

StuartRO

2006 Rho kinase acts at separate steps in ureteric bud and metanephric mesenchyme morphogenesis during kidney development. Differentiation 74 638 647

14. WatanabeT

IchiharaM

HashimotoM

ShimonoK

ShimoyamaY

2002 Characterization of gene expression induced by RET with MEN2A or MEN2B mutation. Am J Pathol 161 249 256

15. CostantiniF

ShakyaR

2006 GDNF/Ret signaling and the development of the kidney. Bioessays 28 117 127

16. CostantiniF

2006 Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation 74 402 421

17. SkinnerMA

LackeyKE

FreemermanAJ

2008 RET activation inhibits doxorubicin-induced apoptosis in SK-N-MC cells. Anticancer Res 28 2019 2025

18. VartiainenMK

MustonenT

MattilaPK

OjalaPJ

ThesleffI

2002 The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics. Mol Biol Cell 13 183 194

19. ZhaoH

KeggH

GradyS

TruongHT

RobinsonML

2004 Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol 276 403 415

20. SainioK

SuvantoP

DaviesJ

WartiovaaraJ

WartiovaaraK

1997 Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development 124 4077 4087

21. PepicelliCV

KispertA

RowitchDH

McMahonAP

1997 GDNF induces branching and increased cell proliferation in the ureter of the mouse. Dev Biol 192 193 198

22. ChiX

HadjantonakisAK

WuZ

HyinkD

CostantiniF

2009 A transgenic mouse that reveals cell shape and arrangement during ureteric bud branching. Genesis 47 61 66

23. PhamH

YuH

LaskiFA

2008 Cofilin/ADF is required for retinal elongation and morphogenesis of the Drosophila rhabdomere. Dev Biol 318 82 91

24. AndrianantoandroE

PollardTD

2006 Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol Cell 24 13 23

25. van RheenenJ

CondeelisJ

GlogauerM

2009 A common cofilin activity cycle in invasive tumor cells and inflammatory cells. J Cell Sci 122 305 311

26. YeP

HabibSL

RiconoJM

KimNH

ChoudhuryGG

2004 Fibronectin induces ureteric bud cells branching and cellular cord and tubule formation. Kidney Int 66 1356 1364

27. de GraaffE

SrinivasS

KilkennyC

D'AgatiV

MankooBS

2001 Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis. Genes Dev 15 2433 2444

28. SchuchardtA

D'AgatiV

Larsson-BlombergL

CostantiniF

PachnisV

1994 Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367 380 383

29. BamburgJR

BernsteinBW

2008 ADF/cofilin. Curr Biol 18 R273 275

30. SrinivasS

GoldbergMR

WatanabeT

D'AgatiV

al-AwqatiQ

1999 Expression of green fluorescent protein in the ureteric bud of transgenic mice: a new tool for the analysis of ureteric bud morphogenesis. Dev Genet 24 241 251

31. BernsteinBW

BamburgJR

2010 ADF/cofilin: a functional node in cell biology. Trends Cell Biol 20 187 195

32. WangW

EddyR

CondeelisJ

2007 The cofilin pathway in breast cancer invasion and metastasis. Nat Rev Cancer 7 429 440

33. YoderA

YuD

DongL

IyerSR

XuX

2008 HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells. Cell 134 782 792

34. EkblomP

1992 Renal Development.

SeldinDW

GiebischG

The Kidney: Physiology and Pathophysiology. Second ed New York Raven Press 475 501

35. LuBC

CebrianC

ChiX

KuureS

KuoR

2009 Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nat Genet 41 1295 1302

36. KuureS

SainioK

VuolteenahoR

IlvesM

WartiovaaraK

2005 Crosstalk between Jagged1 and GDNF/Ret/GFRalpha1 signalling regulates ureteric budding and branching. Mech Dev 122 765 780

37. PachnisV

MankooBS

CostantiniF

1993 Expression of the c-ret proto-oncogene during mouse embryogenesis. Development 119 1005 1017

38. WilkinsonDG

1992 Whole mount in situ hybridization of vertebrate embryos.

WilkinsonDG

In situ hybridization: a practical approach Oxford IRL Press 75 83

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#