Talk:Developmental Signals - Pax

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Cite this page: Hill, M.A. (2021, April 19) Embryology Developmental Signals - Pax. Retrieved from


Anti-EDAR Agonist Antibody Therapy Resolves Palate Defects in Pax9-/- Mice

J Dent Res. 2017 Oct;96(11):1282-1289. doi: 10.1177/0022034517726073. Epub 2017 Aug 16.

Jia S1, Zhou J1, Wee Y1, Mikkola ML2, Schneider P3, D'Souza RN1,4.

Abstract To date, surgical interventions are the only means by which craniofacial anomalies can be corrected so that function, esthetics, and the sense of well-being are restored in affected individuals. Unfortunately, for patients with cleft palate-one of the most common of congenital birth defects-treatment following surgery is prolonged over a lifetime and often involves multidisciplinary regimens. Hence, there is a need to understand the molecular pathways that control palatogenesis and to translate such information for the development of noninvasive therapies that can either prevent or correct cleft palates in humans. Here, we use the well-characterized model of the Pax9-/- mouse, which displays a consistent phenotype of a secondary cleft palate, to test a novel therapeutic. Specifically, we demonstrate that the controlled intravenous delivery of a novel mouse monoclonal antibody replacement therapy, which acts as an agonist for the ectodysplasin (Eda) pathway, can resolve cleft palate defects in Pax9-/- embryos in utero. Such pharmacological interventions did not reverse the arrest in tooth, thymus, and parathyroid gland development, suggesting that the relationship of Pax9 to the Eda/Edar pathway is both unique and essential for palatogenesis. Expression analyses and unbiased gene expression profiling studies offer a molecular explanation for the resolution of palatal defects, showing that Eda and Edar-related genes are expressed in normal palatal tissues and that the Eda/Edar signaling pathway is downstream of Pax9 in palatogenesis. Taken together, our data uncover a unique relationship between Pax9 and the Eda/Edar signaling pathway that can be further exploited for the development of noninvasive, safe, and effective therapies for the treatment of cleft palate conditions and other single-gene disorders affecting the craniofacial complex. KEYWORDS: cleft palate; craniofacial biology/genetics; developmental biology; gene expression; morphogenesis; therapeutic treatment PMID: 28813171 PMCID: PMC5613884 [Available on 2018-10-01] DOI: 10.1177/0022034517726073 [Indexed for MEDLINE]

The Pax gene family: Highlights from cephalopods

PLoS One. 2017 Mar 2;12(3):e0172719. doi: 10.1371/journal.pone.0172719. eCollection 2017.

Navet S1, Buresi A1, Baratte S1,2, Andouche A1, Bonnaud-Ponticelli L1, Bassaglia Y


Pax genes play important roles in Metazoan development. Their evolution has been extensively studied but Lophotrochozoa are usually omitted. We addressed the question of Pax paralog diversity in Lophotrochozoa by a thorough review of available databases. The existence of six Pax families (Pax1/9, Pax2/5/8, Pax3/7, Pax4/6, Paxβ, PoxNeuro) was confirmed and the lophotrochozoan Paxβ subfamily was further characterized. Contrary to the pattern reported in chordates, the Pax2/5/8 family is devoid of homeodomain in Lophotrochozoa. Expression patterns of the three main pax classes (pax2/5/8, pax3/7, pax4/6) during Sepia officinalis development showed that Pax roles taken as ancestral and common in metazoans are modified in S. officinalis, most likely due to either the morphological specificities of cephalopods or to their direct development. Some expected expression patterns were missing (e.g. pax6 in the developing retina), and some expressions in unexpected tissues have been found (e.g. pax2/5/8 in dermal tissue and in gills). This study underlines the diversity and functional plasticity of Pax genes and illustrates the difficulty of using probable gene homology as strict indicator of homology between biological structures.

PMID 28253300 PMCID: PMC5333810 DOI: 10.1371/journal.pone.0172719


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.


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


PMID 24496612

Open Access article distributed under the terms of the Creative Commons Attribution License (

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


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."