Dataset Information

Islet1-mediated activation of the ?-catenin pathway is necessary for hindlimb initiation in mice.

ABSTRACT: The transcriptional basis of vertebrate limb initiation, which is a well-studied system for the initiation of organogenesis, remains elusive. Specifically, involvement of the ?-catenin pathway in limb initiation, as well as its role in hindlimb-specific transcriptional regulation, are under debate. Here, we show that the ?-catenin pathway is active in the limb-forming area in mouse embryos. Furthermore, conditional inactivation of ?-catenin as well as Islet1, a hindlimb-specific factor, in the lateral plate mesoderm results in a failure to induce hindlimb outgrowth. We further show that Islet1 is required for the nuclear accumulation of ?-catenin and hence for activation of the ?-catenin pathway, and that the ?-catenin pathway maintains Islet1 expression. These two factors influence each other and function upstream of active proliferation of hindlimb progenitors in the lateral plate mesoderm and the expression of a common factor, Fgf10. Our data demonstrate that Islet1 and ?-catenin regulate outgrowth and Fgf10-Fgf8 feedback loop formation during vertebrate hindlimb initiation. Our study identifies Islet1 as a hindlimb-specific transcriptional regulator of initiation, and clarifies the controversy regarding the requirement of ?-catenin for limb initiation.

SUBMITTER: Kawakami Y

PROVIDER: S-EPMC3177316 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice.

Kawakami Yasuhiko Y Marti Merce M Kawakami Hiroko H Itou Junji J Quach Thu T Johnson Austin A Sahara Setsuko S O'Leary Dennis D M DD Nakagawa Yasushi Y Lewandoski Mark M Pfaff Samuel S Evans Sylvia M SM Izpisua Belmonte Juan Carlos JC

Development (Cambridge, England) 20111001 20

The transcriptional basis of vertebrate limb initiation, which is a well-studied system for the initiation of organogenesis, remains elusive. Specifically, involvement of the β-catenin pathway in limb initiation, as well as its role in hindlimb-specific transcriptional regulation, are under debate. Here, we show that the β-catenin pathway is active in the limb-forming area in mouse embryos. Furthermore, conditional inactivation of β-catenin as well as Islet1, a hindlimb-specific factor, in the l ...[more]

PMID: 21937598

Similar Datasets

Project description:Estrogen levels decline in both sexes with age, but more dramatically in females. Activation of the Wnt/β-catenin signaling pathway is central to the regulation of bone mass accrual and maintenance and in response to mechanical loading. Using the ovariectomized mouse model we examined the effect of estrogen loss on the osteocyte's ability to activate the Wnt/β-catenin pathway following mechanical loading. Female TOPGAL mice underwent ovariectomy (OVX) (n = 10) or sham surgery (n = 10) at 16 weeks of age. Four weeks post-surgery, a single loading session (global strain of 2200 με for 100 cycles at 2 Hz) was performed on the right forearm with the left as a non-loaded control. Mice (n = 5) were sacrificed at 1 or 24 hr post-load. Ulnae were stained for β-catenin activation, femurs were used for μCT and 3-pt bending/biomechanical testing, and tibiae were used for histology analysis and to determine osteocyte lacunar size using SEM and high resolution micro-XCT. A 2.2-fold increase in β-catenin signaling activation was observed 24 hr post-load in the Sham group but did not occur in the OVX group. The OVX group versus control had significant losses (p < 0.05) in trabecular BMD (-8%), BV/TV (-35%) and thickness (-23%), along with cortical thickness (-6%) and periosteal perimeter (-4%). The OVX group had significantly higher trabecular bone osteoclast numbers (63%), OCS/BS (77%) and N.OC/BPm (94%) and a significant decrease in osteoblast number (53%), OBS/BS (37%) and N.OB/BPm (40%) compared to the sham group (p < 0.05). Cortical bone lacunar number/lacunar volume and bone biomechanical properties did not change between groups. Given that the ulna is a cortical bone loading model and the lack of changes in osteocyte lacunar number/volume in cortical bone, which would alter strains experienced by osteocytes, these data suggest the absence of estrogen resulted in intrinsic changes in the ability of the osteocyte to respond to mechanical load, rather than changes in the biomechanical and architectural properties of bone.

Dataset Information

Islet1-mediated activation of the ?-catenin pathway is necessary for hindlimb initiation in mice.

Publications

Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets