Biology subjects

Kao, T.-J.

Publications and source records attributed to Kao, T.-J..

4 recordsLinked to original sources

bioRxiv2025

Specificity Protein 1 is essential for the limb trajectory of ephrin-mediated spinal motor axons

The precise organization of neural circuits requires highly specific axon guidance, facilitated by cell-surface guidance receptors on axonal growth cones that help neurons reach their target destinations. Despite a limited repertoire of known guidance receptors and ligands, neural systems achieve complex axonal networks, suggesting that additional regulatory mechanisms exist. One proposed strategy is the co-expression of ligands and their receptors on the same axons, allowing modulation of receptor responsiveness to guidance cues. To investigate this mechanism, we studied the spinal lateral motor column (LMC) motor neurons, which make a binary axon pathfinding decision toward limb targets. We hypothesized that specificity protein 1 (Sp1), a transcription factor, regulates ephrin expression in LMC neurons, thereby modulating receptor functions via cis-attenuation to ensure accurate axonal pathfinding. Our results show that Sp1 is indeed expressed in LMC neurons during critical axonal extension periods. Manipulating Sp1 activity disrupted LMC axon trajectory selection, and RNA-Seq analysis indicated that Sp1 regulates genes associated with axon guidance, including ephrins. We found that Sp1 knockdown affected ephrin/Eph cis-binding and trans-signaling, highlighting Sp1s role in controlling axonal projections through ephrin gene regulation. Additionally, coactivators p300 and CBP are essential for Sp1s regulatory function. These findings identify Sp1 as a key transcription factor in LMC neurons, essential for ephrin expression and ephrin/Eph-mediated axon guidance, providing insights into the molecular mechanisms of neural circuit formation.

neuroscience↗

bioRxiv2021

Focused Ultrasound Modulation of Hepatic Neural Plexus Restores Glucose Homeostasis in Diabetes

While peripheral glucose sensors are known to relay signals of substrate availability to integrative nuclei in the brain, the importance of these pathways in maintaining energy homeostasis and their contribution to disease remain unknown. Herein, we demonstrate that selective activation of the hepatoportal neural plexus via transient peripheral focused ultrasound (pFUS) induces glucose homeostasis in models of well-established insulin resistant diabetes. pFUS modulates sensory projections to the hindbrain and alters hypothalamic concentrations of neurotransmitters that regulate metabolism, resulting in potentiation of hypothalamic insulin signaling, leptin-independent inhibition of the orexigenic neuropeptide Y system, and therapeutic alteration in autonomic output to peripheral effector organs. Multiomic profiling confirms pFUS-induced modifications of key metabolic functions in liver, pancreas, muscle, adipose, kidney, and intestines. Activation of the hepatic nutrient sensing pathway not only restores nervous system coordination of peripheral metabolism in three different species but does so across these organ systems; several of which are current targets of antidiabetic drug classes. These results demonstrate the potential of hepatic pFUS as a novel/non-pharmacologic therapeutic modality to restore glucose homeostasis in metabolic diseases, including type II diabetes. One Sentence SummaryWe utilize a non-invasive ultrasound technique to activate a liver-brain sensory pathway and demonstrate its potential to induce durable normalization of glucose homeostasis in models of well-established insulin resistant diabetes.

biophysics↗

bioRxiv2020

A 3D Reconstruction Algorithm for Real-time Simultaneous Multi-Source EIT Imaging for Lung Function Monitoring

Monitoring regional pulmonary ventilation and pulsatile perfusion changes in a 3D region of interest (ROI) of the lung is a promising application for electrical impedance tomography (EIT). This paper describes a 3D analytical reconstruction algorithm that was embedded in a prototype EIT system to enable a real-time image reconstruction at nearly 20 frames per second for monitoring impedance changes in the chest in real-time. The derivation and results of the 3D analytical forward solution and inverse solution and details of the real-time reconstruction algorithm are given. The algorithm and EIT system are validated with simulated data, in-vitro phantoms, and finally shown to be capable of imaging ventilation and pulsatile perfusion in human subjects. The human subject data was obtained using a high-precision, high-speed and simultaneous multiple current source (SMS-EIT) developed by GE Research. Data was collected using four rows of 8 electrodes for a healthy adult male subject and 2 rows of 16 electrodes for six healthy human female subjects, with one row placed above the breasts and a second row placed at the infra-mammary fold. Each of the female subjects performed a breathing maneuver with a volumetric incentive spirometer, and the volume of air inhaled was calculated from the EIT images. Pulsatile perfusion images were computed from this data, and regional lung filling was also analyzed.

bioengineering↗

bioRxiv2019

Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability

Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.

neuroscience↗