Comparative Analysis of cul5 and rbx2 Expression in the Developing and Adult Murine Brain and Their Essentiality During Mouse Embryogenesis

Keiko Hino, Sergi Simo Olivar, Jonathan A. Cooper

Research output: Contribution to journalArticle

Abstract

Background: The E3 Cullin 5-RING ubiquitin ligase (CRL5) is a multiprotein complex that has recently been highlighted as a major regulator of central nervous system development. Cullin 5 (Cul5) and the RING finger protein Rbx2 are two CRL5 core components required for CRL5 function in the brain, but their full expression patterns and developmental functions have not been described in detail. Results: Using a gene-trap mouse model for Cul5 and a knock-in–knockout mouse model for Rbx2, we show that lack of Cul5, but not Rbx2, disrupts blastocyst formation. However, Rbx2 is required for embryo survival at later embryonic stages. We also show that cul5 is expressed in the embryo proper as early as E7.5 and its expression is mostly restricted to the central nervous system and limbs at later time points. Finally, we show that rbx2 and cul5 are co-expressed in most areas of the brain during development and in the adult. Conclusions: Our results show that Cul5, but not Rbx2, is required during early embryogenesis and suggests that Cul5 has Rbx2-independent functions in early development. In the brain, Cul5 and Rbx2 are expressed in a similar fashion, allowing the nucleation of an active CRL5 complex. Developmental Dynamics 247:1227–1236, 2018.

Original languageEnglish (US)
Pages (from-to)1227-1236
Number of pages10
JournalDevelopmental Dynamics
Volume247
Issue number11
DOIs
StatePublished - Nov 1 2018

Fingerprint

Cullin Proteins
Embryonic Development
Brain
Embryonic Structures
Central Nervous System
Multiprotein Complexes
Blastocyst
Ligases
Ubiquitin
Extremities

Keywords

  • brain development
  • CRL5
  • cul5
  • Embryogenesis
  • rbx2

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Comparative Analysis of cul5 and rbx2 Expression in the Developing and Adult Murine Brain and Their Essentiality During Mouse Embryogenesis. / Hino, Keiko; Simo Olivar, Sergi; Cooper, Jonathan A.

In: Developmental Dynamics, Vol. 247, No. 11, 01.11.2018, p. 1227-1236.

Research output: Contribution to journalArticle

@article{6fa326ee5d314dd4b7fd90c4d7487dc4,
title = "Comparative Analysis of cul5 and rbx2 Expression in the Developing and Adult Murine Brain and Their Essentiality During Mouse Embryogenesis",
abstract = "Background: The E3 Cullin 5-RING ubiquitin ligase (CRL5) is a multiprotein complex that has recently been highlighted as a major regulator of central nervous system development. Cullin 5 (Cul5) and the RING finger protein Rbx2 are two CRL5 core components required for CRL5 function in the brain, but their full expression patterns and developmental functions have not been described in detail. Results: Using a gene-trap mouse model for Cul5 and a knock-in–knockout mouse model for Rbx2, we show that lack of Cul5, but not Rbx2, disrupts blastocyst formation. However, Rbx2 is required for embryo survival at later embryonic stages. We also show that cul5 is expressed in the embryo proper as early as E7.5 and its expression is mostly restricted to the central nervous system and limbs at later time points. Finally, we show that rbx2 and cul5 are co-expressed in most areas of the brain during development and in the adult. Conclusions: Our results show that Cul5, but not Rbx2, is required during early embryogenesis and suggests that Cul5 has Rbx2-independent functions in early development. In the brain, Cul5 and Rbx2 are expressed in a similar fashion, allowing the nucleation of an active CRL5 complex. Developmental Dynamics 247:1227–1236, 2018.",
keywords = "brain development, CRL5, cul5, Embryogenesis, rbx2",
author = "Keiko Hino and {Simo Olivar}, Sergi and Cooper, {Jonathan A.}",
year = "2018",
month = "11",
day = "1",
doi = "10.1002/dvdy.24675",
language = "English (US)",
volume = "247",
pages = "1227--1236",
journal = "Developmental Dynamics",
issn = "1058-8388",
publisher = "Wiley-Liss Inc.",
number = "11",

}

TY - JOUR

T1 - Comparative Analysis of cul5 and rbx2 Expression in the Developing and Adult Murine Brain and Their Essentiality During Mouse Embryogenesis

AU - Hino, Keiko

AU - Simo Olivar, Sergi

AU - Cooper, Jonathan A.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: The E3 Cullin 5-RING ubiquitin ligase (CRL5) is a multiprotein complex that has recently been highlighted as a major regulator of central nervous system development. Cullin 5 (Cul5) and the RING finger protein Rbx2 are two CRL5 core components required for CRL5 function in the brain, but their full expression patterns and developmental functions have not been described in detail. Results: Using a gene-trap mouse model for Cul5 and a knock-in–knockout mouse model for Rbx2, we show that lack of Cul5, but not Rbx2, disrupts blastocyst formation. However, Rbx2 is required for embryo survival at later embryonic stages. We also show that cul5 is expressed in the embryo proper as early as E7.5 and its expression is mostly restricted to the central nervous system and limbs at later time points. Finally, we show that rbx2 and cul5 are co-expressed in most areas of the brain during development and in the adult. Conclusions: Our results show that Cul5, but not Rbx2, is required during early embryogenesis and suggests that Cul5 has Rbx2-independent functions in early development. In the brain, Cul5 and Rbx2 are expressed in a similar fashion, allowing the nucleation of an active CRL5 complex. Developmental Dynamics 247:1227–1236, 2018.

AB - Background: The E3 Cullin 5-RING ubiquitin ligase (CRL5) is a multiprotein complex that has recently been highlighted as a major regulator of central nervous system development. Cullin 5 (Cul5) and the RING finger protein Rbx2 are two CRL5 core components required for CRL5 function in the brain, but their full expression patterns and developmental functions have not been described in detail. Results: Using a gene-trap mouse model for Cul5 and a knock-in–knockout mouse model for Rbx2, we show that lack of Cul5, but not Rbx2, disrupts blastocyst formation. However, Rbx2 is required for embryo survival at later embryonic stages. We also show that cul5 is expressed in the embryo proper as early as E7.5 and its expression is mostly restricted to the central nervous system and limbs at later time points. Finally, we show that rbx2 and cul5 are co-expressed in most areas of the brain during development and in the adult. Conclusions: Our results show that Cul5, but not Rbx2, is required during early embryogenesis and suggests that Cul5 has Rbx2-independent functions in early development. In the brain, Cul5 and Rbx2 are expressed in a similar fashion, allowing the nucleation of an active CRL5 complex. Developmental Dynamics 247:1227–1236, 2018.

KW - brain development

KW - CRL5

KW - cul5

KW - Embryogenesis

KW - rbx2

UR - http://www.scopus.com/inward/record.url?scp=85056190068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056190068&partnerID=8YFLogxK

U2 - 10.1002/dvdy.24675

DO - 10.1002/dvdy.24675

M3 - Article

C2 - 30269386

AN - SCOPUS:85056190068

VL - 247

SP - 1227

EP - 1236

JO - Developmental Dynamics

JF - Developmental Dynamics

SN - 1058-8388

IS - 11

ER -