Control of pelvic girdle development by genes of the Pbx family and Emx2

Abstract

Genes expressed in the somatopleuric mesoderm, the embryonic domain giving rise to the vertebrate pelvis, appear important for pelvic girdle formation. Among such genes, Pbx family members and Emx2 were found to genetically interact in hindlimb and pectoral girdle formation. Here, we generated compound mutant embryos carrying combinations of mutated alleles for Pbx1, Pbx2, and Pbx3, as well as Pbx1 and Emx2, to examine potential genetic interactions during pelvic development. Indeed, Pbx genes share overlapping functions and Pbx1 and Emx2 genetically interact in pelvic formation. We show that, in compound Pbx1;Pbx2 and Pbx1;Emx2 mutants, pelvic mesenchymal condensation is markedly perturbed, indicative of an upstream control by these homeoproteins. We establish that expression of Tbx15, Prrx1, and Pax1, among other genes involved in the specification and development of select pelvic structures, is altered in our compound mutants. Lastly, we identify potential Pbx1-Emx2-regulated enhancers for Tbx15, Prrx1, and Pax1, using bioinformatics analyses.

Islet1 regulates establishment of the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory gene network in mouse embryos

“…5D,E,I,J). Pbx genes are important for development of the ilium (Capellini et al, 2011), which was not affected in Hoxb6Cre; Isl1 cKO hindlimbs. These results indicate that Islet1 regulates the ) and Pbx2 (E,J) expression in control (A-E) and mutant (F-J) hindlimb buds at E10.25-11.5.…”

“…As Shh -/-limbs develop normal proximal structures (Chiang et al, 2001;Kraus et al, 2001), the proximal defects are likely to be due to alterations other than the downregulation of Shh. Therefore, we examined expression of some of genes involved in the development of the pelvic girdle (Capellini et al, 2011). Indeed, the expression of Twist1 and Prrx1 in the proximal hindlimb bud was reduced and Pax1 expression was lost in Hoxb6Cre; Isl1 cKO hindlimb buds (Fig.…”

Pbx Regulates Patterning of the Cerebral Cortex in Progenitors and Postmitotic Neurons

“…PBX/EXD proteins form complexes with HOX proteins, and function upstream of Hox genes, and control patterning of the A-P body axis and the limb bud (Capellini et al, 2011b; Vitobello et al, 2011). In addition, mouse Pbx genes have critical functions in regulating spleen, craniofacial, and skeletal development (Capellini et al, 2011a; Ferretti et al, 2011; Koss et al, 2012). …”

Genetics of scapula and pelvis development: An evolutionary perspective

“…As Pbx1 , Emx2 , and Sox9 are expressed in the lateral plate mesoderm and somatopleure, they may also have a major impact on the expression of Fgf10 , which encodes a critical signaling molecule for pelvic morphogenesis. Indeed, Fgf10 −/− mice exhibit a near-total lack of pelvic structures (Sekine et al, 1999), and Fgf10 expression is reduced in Pbx/Emx2 mutants (Capellini et al, 2011, 2010; Capellini and Selleri, unpublished results).…”

“…Based on gene expression studies and histology, this somatopleuric anlagen appears adjacent to the hindlimb bud at E28 in humans (mouse E9.5/10) (Bardeen & Lewis, 1901; Capellini et al, 2011; O’Rahilly & Gardner, 1975) and between E34–36 (mouse E9.5/10–E11.5/12) mesodermal cells condense in a specific region demarcated by the obturator, femoral, and sciatic nerves (Laurenson, 1964a). Shortly after, the mass then begins to expand to form three processes, each of which marks the precursor cell populations of the ilium, ischium, and pubis (Fazekas & Kosa, 1978; Pomikal & Streicher, 2010).…”