International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 91 - REQUIREMENT FOR THE HOX-COFACTOR PBX1 IN SKELETAL PATTERNING AND NORMAL ORGANOGENESIS

Professor Licia Selleri
Institute of Genetic Medicine
"Program of Genetics and Cell Biology of Cornell/Sloan Kettering"
Cornell University Medical School
Whitney W-406, 1300 York Avenue
New York NY 10021
USA

Co-Authors: 1) Depew M, 1)Rubenstein J, 2) Kim S, 3) DiMartino J, 3) Cleary M
Institutions: 1)Nina Ireland Laboratory, UCSF, 2)Department of Developmental Biology, Stanford University, 3)Department of Pathology, Stanford University

Pbx1, homologue of Drosophila EXD, is a TALE (three amino acid loop extension) homeodomain protein.  As a heterodimer with other TALE proteins, Pbx1 binds DNA with Hox proteins that contain tryptophan-bearing dimerization motifs. To present, the lack of Pbx1 germline mutants has compromised the analysis of its in vivo contributions to mammalian development.  We generated and characterized Pbx1-deficient mice.  Pbx1 is an essential gene, whose loss results in embryonic lethality with hypoplasia or aplasia of multiple organs (Selleri et al., Development 126, in press).  A role in patterning is evidenced by widespread defects of the skeleton, including transformation of skeletal elements of the second branchial arch. Absence of Pbx1 results in premature chondrocyte differentiation and reduced proliferation. Marked differences in the proliferative state of chondrocytes were observed by Bromodeoxyuridine (BrdU) in vivo labeling of wt and Pbx1-/- embryos. These studies reveal a novel function of Pbx1 in temporally coordinating the extent of chondrocyte proliferation with terminal differentiation. They parallel our observations that the hematopoietic defect in Pbx1-/- embryos results from deficiencies in the proliferative expansion of hematopoietic progenitor cells (DiMartino, Selleri et al., Blood 98, in press).  Interestingly, the pancreatic hypoplasia and defects in exocrine and endocrine cell differentiation in Pbx1-/- embryos (Kim, Selleri et al., submitted) are also characterized by a reduction of pancreatic cell proliferation. Thus, Pbx1 may serve analogous roles to orchestrate the growth properties of progenitors at specific developmental stages, within multiple cellular lineages. 


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