Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome

Terence D. Capellini, Rediet Zewdu, Giuseppina Di Giacomo, Stefania Asciutti, Jamie E. Kugler, Anna Di Gregorio, Licia Selleri

Research output: Contribution to journalArticle

Abstract

The post-cranial axial skeleton consists of a metameric series of vertebral bodies and intervertebral discs, as well as adjoining ribs and sternum. Patterning of individual vertebrae and distinct regions of the vertebral column is accomplished by Polycomb and Hox proteins in the paraxial mesoderm, while their subsequent morphogenesis depends partially on Pax1/Pax9 in the sclerotome. In this study, we uncover that Pbx1/Pbx2 are co-expressed during successive stages of vertebral and rib development. Next, by exploiting a Pbx1/Pbx2 loss-of-function mouse, we show that decreasing Pbx2 dosage in the absence of Pbx1 affects axial development more severely than single loss of Pbx1. Pbx1/Pbx2 mutants exhibit a homogeneous vertebral column, with loss of vertebral identity, rudimentary ribs, and rostral hindlimb shifts. Of note, these axial defects do not arise from perturbed notochord function, as cellular proliferation, apoptosis, and expression of regulators of notochord signaling are normal in Pbx1/Pbx2 mutants. While the observed defects are consistent with loss of Pbx activity as a Hox-cofactor in the mesoderm, we additionally establish that axial skeletal patterning and hindlimb positioning are governed by Pbx1/Pbx2 through their genetic control of Polycomb and Hox expression and spatial distribution in the mesoderm, as well as of Pax1/Pax9 in the sclerotome.

Original languageEnglish (US)
Pages (from-to)500-514
Number of pages15
JournalDevelopmental Biology
Volume321
Issue number2
DOIs
StatePublished - Sep 15 2008

Fingerprint

Ribs
Mesoderm
Notochord
Spine
Hindlimb
Sternum
Intervertebral Disc
Morphogenesis
Skeleton
Cell Proliferation
Apoptosis
Proteins

Keywords

  • Axial skeleton
  • Hox
  • Limb position
  • Meis/Prep
  • Notochord
  • Pax
  • Pbx
  • Polycomb
  • Sclerotome
  • Vertebrae

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. / Capellini, Terence D.; Zewdu, Rediet; Di Giacomo, Giuseppina; Asciutti, Stefania; Kugler, Jamie E.; Di Gregorio, Anna; Selleri, Licia.

In: Developmental Biology, Vol. 321, No. 2, 15.09.2008, p. 500-514.

Research output: Contribution to journalArticle

Capellini, Terence D. ; Zewdu, Rediet ; Di Giacomo, Giuseppina ; Asciutti, Stefania ; Kugler, Jamie E. ; Di Gregorio, Anna ; Selleri, Licia. / Pbx1/Pbx2 govern axial skeletal development by controlling Polycomb and Hox in mesoderm and Pax1/Pax9 in sclerotome. In: Developmental Biology. 2008 ; Vol. 321, No. 2. pp. 500-514.
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