BMP9 stimulates joint regeneration at digit amputation wounds in mice.

A major goal of regenerative medicine is to stimulate tissue regeneration after traumatic injury. We previously discovered that treating digit amputation wounds with BMP2 in neonatal mice stimulates endochondral ossification to regenerate the stump bone. Here we show that treating the amputation wound with BMP9 stimulates regeneration of a synovial joint that forms an articulation with the stump bone.

The periosteal requirement and temporal dynamics of BMP2-induced middle phalanx regeneration in the adult mouse.

Regeneration of mammalian limbs is restricted to amputation of the distal digit tip, the terminal phalanx (P3). The adjacent skeletal element, the middle phalanx (P2), has emerged as a model system to investigate regenerative failure and as a site to test approaches aimed at enhancing regeneration. We report that exogenous application of bone morphogenetic protein 2 (BMP2) stimulates the formation of a transient cartilaginous callus distal to the amputation plane that mediates the regeneration of the amputated P2 bone.

Angiogenesis is inhibitory for mammalian digit regeneration.

The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti-angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M.

The mouse digit tip: from wound healing to regeneration.

A challenge to the study of regeneration is determining at what point the processes of wound healing and regeneration diverge. The mouse displays level-specific regeneration responses. An amputation through the distal third of the terminal phalanx will prompt a regeneration response and result in a new digit tip that mimics the morphology of the lost digit tip.

SDF-1α/CXCR4 signaling mediates digit tip regeneration promoted by BMP-2.

Previously we demonstrated that BMP signaling is required for endogenous digit tip regeneration, and that treatment with BMP-2 or -7 induces a regenerative response following amputation at regeneration-incompetent levels (Yu et al., 2010, 2012). Both endogenous regeneration and BMP-induced regeneration are associated with the transient formation of a blastema, however the formation of a regeneration blastema in mammals is poorly understood.

Dlx5 and Msx2 regulate mouse anterior neural tube closure through ephrinA5-EphA7.

Homeodomain-containing transcription factors Dlx5 and Msx2 are able to form a heterodimer, and together can regulate embryonic development including skeletogenesis. Dlx5 functions as a transcriptional activator and Msx2 a transcriptional repressor, and they share common target genes. During mouse digit development, the expression domains of Dlx5 and Msx2 overlap at the distal region of the developing terminal phalange, although digit formation and regeneration are not altered in the Dlx5 and Msx2 null mutant embryos.

Connective tissue fibroblast properties are position-dependent during mouse digit tip regeneration.

A key factor that contributes to the regenerative ability of regeneration-competent animals such as the salamander is their use of innate positional cues that guide the regeneration process. The limbs of mammals has severe regenerative limitations, however the distal most portion of the terminal phalange is regeneration competent. This regenerative ability of the adult mouse digit is level dependent: amputation through the distal half of the terminal phalanx (P3) leads to successful regeneration, whereas amputation through a more proximal location, e.

BMP2 induces segment-specific skeletal regeneration from digit and limb amputations by establishing a new endochondral ossification center.

Bone morphogenetic proteins (BMPs) are required for bone development, the repair of damage skeletal tissue, and the regeneration of the mouse digit tip. Previously we showed that BMP treatment can induce a regeneration response in mouse digits amputated at a proximal level of the terminal phalangeal element (P3) (Yu et al., 2010).

High quality RNA isolation from Aedes aegypti midguts using laser microdissection microscopy.

Background: Laser microdissection microscopy (LMM) has potential as a research tool because it allows precise excision of target tissues or cells from a complex biological specimen, and facilitates tissue-specific sample preparation. However, this method has not been used in mosquito vectors to date. To this end, we have developed an LMM method to isolate midgut RNA using Aedes aegypti.

Wound healing and blastema formation in regenerating digit tips of adult mice.

Amputation of the distal region of the terminal phalanx of mice causes an initial wound healing response followed by blastema formation and the regeneration of the digit tip. Thus far, most regeneration studies have focused in embryonic or neonatal models and few studies have examined adult digit regeneration. Here we report on studies that include morphological, immunohistological, and volumetric analyses of adult digit regeneration stages.

BMP signaling induces digit regeneration in neonatal mice.

The regenerating digit tip of mice is a novel epimorphic response in mammals that is similar to fingertip regeneration in humans. Both display restricted regenerative capabilities that are amputation-level dependent. Using this endogenous regeneration model in neonatal mice, we have found that noggin treatment inhibits regeneration, thus suggesting a bone morphogenetic protein (BMP) requirement.

Mammalian regeneration and regenerative medicine.

Mammals are generally considered to be poor regenerators, yet there are a handful of mammalian models that display a robust ability to regenerate. One such system is the regenerating tips of digits in both humans and mice. In vitro studies of regenerating fetal human and mouse digit tips display both anatomical and molecular similarities, indicating that the mouse digit is a clinically relevant model.

Development and regeneration of the neonatal digit tip in mice.

The digit tips of children and rodents are known to regenerate following amputation. The skeletal structure that regenerates is the distal region of the terminal phalangeal bone that is associated with the nail organ. The terminal phalanx forms late in gestation by endochondral ossification and continues to elongate until sexual maturity (8 weeks of age).

Limb regeneration in higher vertebrates: developing a roadmap.

We review what is known about amphibian limb regeneration from the prospective of developing strategies for the induction of regeneration in adult mammals. Prominent in urodele amphibian limb regeneration is the formation of a blastema of undifferentiated cells that goes on to reform the limb. The blastema shares many properties with the developing limb bud; thus, the outgrowth phase of regeneration can be thought of as cells going through development again, i.

Digit regeneration is regulated by Msx1 and BMP4 in fetal mice.

The regeneration of digit tips in mammals, including humans and rodents, represents a model for organ regeneration in higher vertebrates. We had previously characterized digit tip regeneration during fetal and neonatal stages of digit formation in the mouse and found that regenerative capability correlated with the expression domain of the Msx1 gene. Using the stage 11 (E14.