Biology subjects

Kaback, D.

Publications and source records attributed to Kaback, D..

4 recordsLinked to original sources

bioRxiv2026

Conditional replacement of the mouse LH receptor with GFP, enabling imaging of cell migration during ovulation

To facilitate the investigation of signaling by the luteinizing hormone receptor (LHR), we created a mouse line called Lhr-COIN. This line allows for the conditional replacement of the Lhr coding sequence with enhanced green fluorescent protein (eGFP), resulting in both a conditional knockout line and a reporter line. By breeding these mice with mice expressing Cre recombinase, we generated mice in which either one or both Lhr alleles were replaced with eGFP. Notably, mice in which one Lhr allele in the granulosa cells was replaced with eGFP exhibited normal LH responsiveness. This enabled live imaging of LH-induced migration of LH-receptor-expressing granulosa cells within preovulatory ovarian follicles. The Lhr-COIN mouse line holds significant potential for future research on LHR function and localization in the ovary and other tissues.

developmental biology↗

bioRxiv2025

Melatonin Enhances Sleep via MT1-Driven Activation of Slo1 in Suprachiasmatic Nucleus Neurons

Melatonin promotes sleep through mechanisms that have remained elusive. Here, we identify a molecular pathway by which melatonin promotes sleep by activating BK channels (Slo1) via MT1 receptors in the suprachiasmatic nucleus (SCN), the brains master circadian clock. In melatonin-proficient CBA/CaJ mice, knockout of either MT1 or Slo1 reduces REM and NREM sleep during the rest phase (daytime), accompanied by prolonged action potentials and diminished afterhyperpolarization in SCN neurons. These electrophysiological and behavioral changes are minimal during the active phase (nighttime). Strikingly, Slo1 expression in the SCN peaks during the daytime, contrary to previous reports, but aligning with its sleep-promoting function. Slo1, but not MT1, deletion also triggers spontaneous seizures, highlighting broader functions beyond circadian control. Structural mapping identifies critical domains mediating MT1-Slo1 coupling. Together, these findings position the MT1-Slo1 signaling axis as a core circadian mechanism linking melatonin to sleep regulation and a potential therapeutic target for sleep disorders.

neuroscience↗

bioRxiv2024

Bovine Formative Embryonic Stem Cell Plasticity in Embryonic and Extraembryonic Differentiation

Bovine embryonic stem cells (bESCs) can greatly enhance understanding of bovine embryonic development and applications for disease-resistance, biomedical and zoonotic pre-clinical models. However, formative bESCs with distinct morphology and complete differentiation capacity are still unreported. We document here the generation of bESCs which are pluripotent both in vitro and in vivo, and efficiently converted into neural progenitor cells (NPCs) and primordial germ cell-like cells (PGCLCs) by direct differentiation. These cells exhibited distinct metabolic features from human and mouse ESCs and early embryos. Formative bESCs contributed to a wide range of cell types within embryonic and extraembryonic tissues after aggregating with mouse and bovine embryos. The establishment of bovine formative ESCs with dual developmental plasticity represents a milestone for agricultural biotechnology and decoding the underlying mechanism of bona fide bovine pluripotency. Summary statementGenerating bovine ESCs would greatly enhance understanding of bovine embryonic development and bioengineering of cattle for disease-resistance, biomedical and zoonotic pre-clinical models.

developmental biology↗

bioRxiv2017

Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor

Activating mutations in fibroblast growth factor (FGF) receptor 3 and inactivating mutations in the NPR2 guanylyl cyclase cause similar forms of dwarfism, but how these two signaling systems interact to regulate bone growth is poorly understood. Here, by use of a mouse model in which NPR2 cannot be dephosphorylated, we show that bone elongation is opposed when NPR2 is dephosphorylated and thus produces less cyclic GMP. By developing an in vivo imaging system to measure cyclic GMP levels in intact tibia, we show that FGF-induced dephosphorylation of NPR2 decreases its guanylyl cyclase activity in growth plate chondrocytes in living bone. Thus FGF signaling lowers cyclic GMP in the growth plate, which counteracts bone elongation. These results define a new component of the signaling network by which activating mutations in the FGF receptor inhibit bone growth.

developmental biology↗