Talk:Developmental Signals - Pax

2014

Pax genes: regulators of lineage specification and progenitor cell maintenance

Development. 2014 Feb;141(4):737-51. doi: 10.1242/dev.091785.

Blake JA, Ziman MR.

Abstract

Pax genes encode a family of transcription factors that orchestrate complex processes of lineage determination in the developing embryo. Their key role is to specify and maintain progenitor cells through use of complex molecular mechanisms such as alternate RNA splice forms and gene activation or inhibition in conjunction with protein co-factors. The significance of Pax genes in development is highlighted by abnormalities that arise from the expression of mutant Pax genes. Here, we review the molecular functions of Pax genes during development and detail the regulatory mechanisms by which they specify and maintain progenitor cells across various tissue lineages. We also discuss mechanistic insights into the roles of Pax genes in regeneration and in adult diseases, including cancer. KEYWORDS: Embryogenesis; Lineage determination; Pax genes

Review

PMID 24496612

http://dev.biologists.org/content/141/4/737.full

Loss of function of mouse Pax-Interacting Protein 1-associated glutamate rich Protein 1a (pagr1a) leads to reduced BMP2 expression and defects in chorion and amnion development

Dev Dyn. 2014 Mar 15. doi: 10.1002/dvdy.24125. [Epub ahead of print]

Kumar A1, Lualdi M, Loncarek J, Cho YW, Lee JE, Ge K, Kuehn MR. Author information

Abstract

Background: Human PAX-Interacting Protein 1 (PAXIP1)-associated glutamate rich protein 1 (PAGR1, also known as PA1) originally was discovered as part of a complex containing PAXIP1 and histone H3K4 methyltransferases MLL3 and MLL4, suggesting a role in epigenetic gene regulation. Further in vitro studies suggested additional functions in DNA damage repair and transcription. However, in vivo analysis of PAGR1 function has been lacking. Results: Here we show that expression of the cognate mouse gene, Pagr1a, is found predominately in the extraembryonic and chorionic ectoderm from pre-gastrulation stages and is upregulated within the embryo proper after gastrulation. Embryos with a germ line deletion of Pagr1a establish the anterior-posterior axis, and show normal neuroectodermal, mesodermal, and endodermal patterning, but fail to develop beyond the 4 to 5 somite stage or to undergo axial rotation. Pagr1a-/- embryos also show abnormal development of extraembryonic tissues with defects seen in the amnion, chorion and visceral yolk sac. At the molecular level, Pagr1a-/- embryos have reduced expression of BMP2, a known regulator of extraembryonic development. Conclusions: Loss of mouse Pagr1a function leads to defective extraembryonic development, likely due at least in part to altered BMP signaling, contributing to developmental arrest. Developmental Dynamics, 2014. © 2014 Wiley Periodicals, Inc. ©2014. Wiley Periodicals, Inc. KEYWORDS: Amniochorionic fold, Amnion, BMP signaling, Chorion

PMID 24633704

Evolution of developmental roles of Pax2/5/8 paralogs after independent duplication in urochordate and vertebrate lineages

"Gene duplication provides opportunities for lineage diversification and evolution of developmental novelties. Duplicated genes generally either disappear by accumulation of mutations (nonfunctionalization), or are preserved either by the origin of positively selected functions in one or both duplicates (neofunctionalization), or by the partitioning of original gene subfunctions between the duplicates (subfunctionalization). The Pax2/5/8 family of important developmental regulators has undergone parallel expansion among chordate groups. After the divergence of urochordate and vertebrate lineages, two rounds of independent gene duplications resulted in the Pax2, Pax5, and Pax8 genes of most vertebrates (the sister group of the urochordates), and an additional duplication provided the pax2a and pax2b duplicates in teleost fish. Separate from the vertebrate genome expansions, a duplication also created two Pax2/5/8 genes in the common ancestor of ascidian and larvacean urochordates."

http://www.biomedcentral.com/1741-7007/6/35