BMP signaling plays important roles in many embryonic developmental processes. Alk3 is one of two BMP type I receptors that transduces BMP signal from the cell surface into cell. Conventional knockout of Alk3 resulted in early embryonic lethality around E7.5-E9.5. In this study, we have generated embryonic mesoderm-specific Alk3 conditional knockout by crossing Dermo1-Cre and floxed Alk3 mice. Abrogation of Alk3-mediated BMP signaling in this mouse resulted in severe defect of secondary ventral body wall formation, replicating the omphalocele phenotype in human. Our finding suggests that Alk3 plays an essential role in the formation of embryonic ventral abdominal wall, and abrogation of BMP signaling activity due to gene mutations in its signaling components could be one of the underlying causes of omphalocele at birth.
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http://dx.doi.org/10.1016/j.bbrc.2007.06.049 | DOI Listing |
Nat Commun
January 2025
Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, and Eph/Ephrin, which dictates cell positioning along the crypt-villus axis. However, studying how the spatial distributions of these signals influences crypt-villus organization is challenging both in vitro and in vivo.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Northwestern University, Chicago, IL, USA.
Background: Apolipoprotein E4 (E4) is the strongest genetic risk factor for sporadic Alzheimer's Disease (AD), and aging is the greatest overall risk factor for AD. Many cellular and molecular changes occur within the brain throughout aging, one of which being the increased bone morphogenetic protein 4 (BMP4) signaling. As APOE and BMPs are known to interact in non-neuronal organs, we hypothesized that enhanced BMP signaling in the brain may interact with APOE in a genotype-dependent manner to initiate or exacerbate neuropathological cascades relevant to AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Northwestern University, Chicago, IL, USA.
Background: Aging is the most significant risk factor for neurodegenerative tauopathies, including Alzheimer's disease (AD), frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and others. However, no specific age-related molecular change in the brain has been identified that leads to disease onset and progression. We have found age-related increases in bone morphogenic protein (BMP) signaling in both human and mouse brains.
View Article and Find Full Text PDFNat Commun
January 2025
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
A balance between stem cell self-renewal and differentiation is required to maintain concurrent proliferation and cellular diversification in organoids; however, this has proven difficult in homogeneous cultures devoid of in vivo spatial niche gradients for adult stem cell-derived organoids. In this study, we leverage a combination of small molecule pathway modulators to enhance the stemness of organoid stem cells, thereby amplifying their differentiation potential and subsequently increasing cellular diversity within human intestinal organoids without the need for artificial spatial or temporal signaling gradients. Moreover, we demonstrate that this balance between self-renewal and differentiation can be effectively and reversibly shifted from secretory cell differentiation to the enterocyte lineage with enhanced proliferation using BET inhibitors, or unidirectional differentiation towards specific intestinal cell types by manipulating in vivo niche signals such as Wnt, Notch, and BMP.
View Article and Find Full Text PDFBone Res
January 2025
Department of Periodontics & Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification (HO). Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO. This study focuses on the ability of the collagen receptor, discoidin domain receptor 2 (DDR2), to regulate BMP activity.
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