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Developing tissues interpret dynamic changes in morphogen activity to generate cell type diversity. To quantitatively study bone morphogenetic protein (BMP) signaling dynamics in the mouse neural tube, we developed an embryonic stem cell differentiation system tailored for growing tissues. Differentiating cells form striking self-organized patterns of dorsal neural tube cell types driven by sequential phases of BMP signaling that are observed both in vitro and in vivo. Data-driven biophysical modeling showed that these dynamics result from coupling fast negative feedback with slow positive regulation of signaling by the specification of an endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling in space, we identify a BMP signaling relay that operates in time. This mechanism allows for a rapid initial concentration-sensitive response that is robustly terminated, thereby regulating balanced sequential cell type generation. Our study provides an experimental and theoretical framework to understand how signaling dynamics are exploited in developing tissues.
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http://dx.doi.org/10.1016/j.devcel.2024.10.024 | DOI Listing |
Case Rep Genet
December 2024
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan.
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder caused by heterozygous pathogenic variants and is characterized by both progressive heterotopic ossification of the soft tissues and congenital malformations of the great toe. In addition to pathological skeletal metamorphosis, patients with FOP experience diverse neurological symptoms such as chronic pain and involuntary movements; however, little is known about the association between FOP and epileptic seizures. We report the case of a young boy with FOP who sustained multiple major fractures due to epileptic loss of consciousness.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Objective: Spinal cord injury (SCI) is a severe and permanent nerve damage condition that poses significant burdens on individuals and society. Various therapeutic approaches have been explored to mitigate the consequences of SCI. Tissue engineering and regenerative medicine have emerged as a promising avenue for addressing this issue.
View Article and Find Full Text PDFInt J Cardiol Congenit Heart Dis
September 2024
VPD Heart and Lung Research Institute, University of Cambridge, United Kingdom.
Pulmonary hypertension (PH) encompasses a group of conditions which ultimately lead to elevated pulmonary arterial pressure. PH is classified into five subgroups, of which Group 1 pulmonary arterial hypertension (PAH), is the most extensively studied. Numerous causal genes have been identified in PAH, most notably germline mutations in bone morphogenetic protein receptor type 2 () and the wider BMP pathway.
View Article and Find Full Text PDFJ Cell Physiol
December 2024
Department of Medical Research and Development, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.
Excessive mechanical overloading of articular cartilage caused by excessive exercise or severe trauma is considered a critical trigger in the development of osteoarthritis (OA). However, the available clinical theranostic molecular targets and underlying mechanisms still require more elucidation. Here, we aimed to examine the possibility that bone morphogenetic proteins (BMPs) serve as molecular targets in rat cartilages and human chondrocytes under conditions of excessive mechanical overloading.
View Article and Find Full Text PDFJ Oral Biosci
December 2024
Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan. Electronic address:
Objective: This study aimed to evaluate the role of the chromodomain helicase DNA-binding protein 3 (CHD3) in tooth morphogenesis in Chd3 knockout mice.
Methods: Chd3 knockout mice were generated using the CRISPR-Cas9 method. Mandibular first molars were extracted from the mice and their littermates and morphometrically analyzed.
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