title: Bmp-4 requires the presence of the digits to initiate programmed cell death in limb interdigital tissues.
abstract: The effects of Bmp-4 on interdigital cell death were investigated in the mouse. Affi-Gel beads, loaded with recombinant Bmp-4 protein, were transplanted into the interdigital tissues of day 12.5 hindlimb, ex utero. It was established that Bmp-4 could induce precocious interdigital cell death. Using in situ hybridization, the expression patterns of bmp-4 and alk-6 receptor were established. Both genes were found coexpressed in the interdigital region of 12.5- and 13. 5-day hindlimbs. This suggests that Bmp-4 may act in an autocrine fashion. We have also studied the effects of Bmp-4 on 12.5-day interdigital tissue cultures. In all specimens examined, the interdigital tissues produced cartilage instead of participating in cell death. The addition of exogenous Bmp-4 to the interdigital cultures did not induce apoptosis but instead enhanced chondrogenesis. The discrepancy between the effects of Bmp-4 in vitro and ex utero was attributed to the presence of digits. When a flanking digit was left attached to the interdigital tissues, in vitro, Bmp-4 promoted apoptosis instead of chondrogenesis. In sum, the results suggest that Bmp-4 is a multifunctional protein and its effect on the interdigital tissues is dependent on the modulating influence of the digits.
authors.affiliation: Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Peoples' Republic of China.
authors.forename: M K
authors.initials: MK
authors.lastname: Tang
authors.forename: A K
authors.initials: AK
authors.lastname: Leung
authors.forename: W H
authors.initials: WH
authors.lastname: Kwong
authors.forename: P H
authors.initials: PH
authors.lastname: Chow
authors.forename: J Y
authors.initials: JY
authors.lastname: Chan
authors.forename: V
authors.initials: V
authors.lastname: Ngo-Muller
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: K K
authors.initials: KK
authors.lastname: Lee
mesh_terms: D029404:Activin Receptors; D000818:Animals; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000302:isolation & purification*; D006614:Hindlimb / Q000196:embryology*; D051379:Mice; D008813:Mice, Inbred ICR; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000302:isolation & purification; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000302:isolation & purification*; D014018:Tissue Distribution; D014034:Toes / Q000196:embryology*
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors