Phactr4 regulates neural tube and optic fissure closure by controlling PP1-, Rb-, and E2F1-regulated cell-cycle progression Journal Article

  

Authors:	Kim, T. H.; Goodman, J.; Anderson, K. V.; Niswander, L.
Article Title:	Phactr4 regulates neural tube and optic fissure closure by controlling PP1-, Rb-, and E2F1-regulated cell-cycle progression
Abstract:	Here we identify the humpty dumpty (humdy) mouse mutant with failure to close the neural tube and optic fissure, causing exencephaly and retinal coloboma, common birth defects. The humdy mutation disrupts Phactr4, an uncharacterized protein phosphatase 1 (PP1) and actin regulator family member, and the missense mutation specifically disrupts binding to PP1. Phactr4 is initially expressed in the ventral cranial neural tube, a region of regulated proliferation, and after neural closure throughout the dorsoventral axis. humdy embryos display elevated proliferation and abnormally phosphorylated, inactive PP1, resulting in Rb hyperphosphorylation, derepression of E2F targets, and abnormal cell-cycle progression. Exencephaly, coloboma, and abnormal proliferation in humdy embryos are rescued by loss of E2f1, demonstrating the cell cycle is the key target controlled by Phactr4. Thus, Phactr4 is critical for the spatially and temporally regulated transition in proliferation through differential regulation of PP1 and the cell cycle during neurulation and eye development. © 2007 Elsevier Inc. All rights reserved.
Keywords:	protein expression; protein phosphorylation; unclassified drug; missense mutation; nonhuman; mouse; phenotype; mouse mutant; animals; mice; cell cycle progression; cell division; embryo; protein targeting; mice, mutant strains; protein binding; cell differentiation; phosphorylation; nuclear proteins; gene expression regulation, developmental; cellular distribution; retina; devbio; cellcycle; f actin; actins; retinoblastoma protein; transcription factor e2f1; neural tube; phosphoprotein phosphatase; eye development; neural tube defect; mice, inbred c3h; e2f1 transcription factor; neurulation; phosphoprotein phosphatase 1; neural tube defects; protein phactr4; coloboma; exencephaly
Journal Title:	Developmental Cell
Volume:	13
Issue:	1
ISSN:	1534-5807
Publisher:	Cell Press
Date Published:	2007-07-01
Start Page:	87
End Page:	102
Language:	English
DOI:	10.1016/j.devcel.2007.04.018
PUBMED:	17609112
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-34347232361&partnerID=40&md5=877970197f9dc1733d9476729fd3cb2e
Notes:	--- - "Cited By (since 1996): 20" - "Export Date: 17 November 2011" - "CODEN: DCEEB" - "Source: Scopus"

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