Article
Developmental Biology
Benoit Haerlingen, Robert Opitz, Isabelle Vandernoot, Angelo Molinaro, Meghna Parakkal Shankar, Pierre Gillotay, Achim Trubiroha, Sabine Costagliola
Summary: Thyroid tissue is derived from ventral pharyngeal endoderm and defects in morphogenesis are a main cause of congenital thyroid diseases. Recent studies have revealed the importance of FGF and BMP signaling in thyroid specification, but the relationship between signaling cues and thyroid transcription factors is still unclear. By analyzing zebrafish embryos, researchers identified a population of Pax2a-expressing thyroid progenitor cells that show enhanced FGF signaling but lack Nkx2.4b expression and BMP signaling. Manipulation of FGF/BMP activities suggests that FGF signaling mainly regulates Pax2a expression, while BMP signaling regulates both Pax2a and Nkx2.4b expression. Similar expression dynamics were observed in mouse embryos, indicating that this refined model of thyroid cell specification is evolutionarily conserved in mammals.
Article
Marine & Freshwater Biology
Sujian Tan, Pin Huan, Baozhong Liu
Summary: This study reveals a functional role of FGFR in organizer specification and dorsal-ventral patterning of Lottia embryos, and indicates that these developmental functions have different sensitivities to FGFR/MAPK signaling.
MARINE LIFE SCIENCE & TECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Farideh Moeinvaziri, Ibrahim Zarkesh, Paria Pooyan, Desmond A. Nunez, Hossein Baharvand
Summary: The inner ear is a complex organ that encodes sound, motion, and orientation in space, with its blood supply playing a pivotal role in growth, maturation, and survival of inner ear tissues. Inner ear organoid models are a promising tool to advance the study of multiple aspects of the inner ear to aid the development of new treatments.
Article
Genetics & Heredity
Le Sun, Lu Ping, Ruzhen Gao, Bo Zhang, Xiaowei Chen
Summary: This study aimed to investigate the role of LMO4 in zebrafish inner ear development. The results showed that lmo4a was constitutively expressed in the otic placode and otic vesicle during the early stages of zebrafish development, and knockdown and knockout of lmo4a resulted in smaller otocysts, fewer hair cells, immature statoacoustic ganglion, and malformed semicircular canals. Further analysis revealed that lmo4a had a regulatory effect on the Bmp pathway and was required for the normal development of zebrafish inner ear.
Article
Cell Biology
Magdalena Zak, Thea Stole, Vincent Plagnol, Nicolas Daudet
Summary: This study investigates the transcriptional effectors and targets of the Notch and Wnt pathways in the embryonic chicken otic vesicle. The results show that inhibition of Notch pathway leads to rapid changes in the expression of neurogenesis-related genes, while the Wnt pathway is associated with numerous genes involved in neurosensory biological function. Additionally, gain-of-function screenings suggest that the endogenous programs of otic neurosensory specification are robust and relatively unaffected by overexpression of a single factor.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Ning Yin, Jingjing Zhao, Panpan Zhang, Baofu Yu, Renjie Chai, Geng-Lin Li
Summary: Hearing loss, predominantly caused by gene mutations, is a common neurosensory disorder. This study used knock-out and point mutation mice as models to investigate the synaptic changes in inner hair cells related to the complex mechanisms of MYO6 mutations. The results reveal altered exocytosis and calcium influx in both immature and mature hair cells, providing insights for the diagnosis and treatment of deafness.
CELL DEATH DISCOVERY
(2023)
Article
Cell & Tissue Engineering
Aleta R. Steevens, Matthew W. Griesbach, Yun You, James R. Dutton, Walter C. Low, Peter A. Santi
Summary: This study successfully produced induced pluripotent stem cell-derived inner ear sensory neurons in a mouse model using blastocyst complementation. The approach not only corrected non-sensory deficits associated with Neurog1 heterozygosity, but also highlighted blastocyst complementation as a potential tool for creating chimeric inner ear cell types for transplantation into damaged inner ears to improve hearing.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Neurosciences
Zachary A. Stoner, Elizabeth M. Ketchum, Sydney Sheltz-Kempf, Paige V. Blinkiewicz, Karen L. Elliott, Jeremy S. Duncan
Summary: It is discovered that Wnt/PCP signaling plays a critical role in the development of inner ear neurons and affects the guidance of inner ear afferents. Through experiments on mice, it is found that Fzd3 has a cell autonomous regulation effect on the guidance of inner ear afferents.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Ludovica Cotellessa, Federica Marelli, Paolo Duminuco, Michela Adamo, Georgios E. . Papadakis, Lucia Bartoloni, Naoko Sato, Mariarosaria Lang-Muritano, Amineh Troendle, Waljit S. . Dhillo, Annamaria Morelli, Giulia Guarnieri, Nelly Pitteloud, Luca Persani, Marco Bonomi, Paolo Giacobini, Valeria Vezzoli
Summary: Fertility in vertebrate species is controlled by GnRH neurons, which arise outside the central nervous system and migrate into the forebrain during development. Genetic disorders associated with infertility, such as CHH and Kallmann syndrome, are characterized by defects in GnRH neuron migration. The study found that Jag1/Notch signaling is involved in the development of GnRH neurons, and JAG1 insufficiency may contribute to the pathogenesis of CHH in humans.
Article
Cell & Tissue Engineering
Yujie Fan, James Hackland, Arianna Baggiolini, Lin Y. Hung, Huiyong Zhao, Paul Zumbo, Polina Oberst, Andrew P. Minotti, Emiliano Hergenreder, Sarah Najjar, Zixing Huang, Nelly M. Cruz, Aaron Zhong, Mega Sidharta, Ting Zhou, Elisa de Stanchina, Doron Betel, Richard M. White, Michael Gershon, Kara Gross Margolis, Lorenz Studer
Summary: We derived sacral enteric nervous system (ENS) precursors from human PSCs through timed exposure to FGF, WNT, and GDF11, enabling posterior patterning and transition from posterior trunk to sacral NC identity. Our study showed that both trunk and sacral NC emerge from a double-positive neuro-mesodermal progenitor (NMP) using a specific reporter hPSC line. Vagal and sacral NC precursors exhibit distinct neuronal subtypes and migratory behaviors, and xenografting of both lineages rescues a mouse model of total aganglionosis, suggesting potential therapeutic interventions for severe forms of Hirschsprung's disease.
Article
Multidisciplinary Sciences
Charles Petitpre, Louis Faure, Phoebe Uhl, Paula Fontanet, Iva Filova, Gabriela Pavlinkova, Igor Adameyko, Saida Hadjab, Francois Lallemend
Summary: This study used deep, single-cell transcriptomics to investigate the molecular mechanisms that govern the identity and organization of spiral ganglion neurons (SGNs) in mice. The study identified a core set of temporally patterned genes and gene regulatory networks that contribute to the diversification of SGNs through sequential binary decisions. The results also revealed that cell-cell signaling is potentially involved in the differentiation of SGNs.
NATURE COMMUNICATIONS
(2022)
Article
Cell & Tissue Engineering
Pei-Ciao Tang, Li Chen, Sunita Singh, Andrew K. Groves, Karl R. Koehler, Xue Zhong Liu, Rick F. Nelson
Summary: In this study, we used stem cell-derived organoids to investigate the effects of Wnt signaling on early placodal ectoderm (PPE) differentiation. We found that modulating Wnt signaling can significantly increase the efficiency and reproducibility of inner ear organoid induction. Our data also reveal the critical role of Wnt signaling in the regionalization of PPE.
Article
Neurosciences
Judith S. Kempfle, Marlon Duro, Andrea Zhang, Carolina D. Amador, Richard Kuang, Ryan Lu, Boris A. Kashemirov, Albert S. Edge, Charles E. McKenna, David H. Jung
Summary: Sensorineural hearing loss is linked to the loss of spiral ganglion neurons and sensory hair cells in the inner ear. The use of neurotrophic factors in the inner ear has shown promise in promoting survival of SGNs and re-wiring of sensory hair cells, with NT-3 and BDNF being key factors in this process. Our study demonstrates the potential of small molecule analogues like 1Aa and Ris-1Aa to stimulate SGNs and promote synaptic regeneration, suggesting a novel strategy for delivering neurotrophic agents to SGNs in cochlear bone.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Hailun Zhu, Sihai Dave Zhao, Alokananda Ray, Yu Zhang, Xin Li
Summary: In this study, the authors used single-cell RNA sequencing to analyze the gene expression patterns in Drosophila neural progenitors and identified a gene regulatory network that controls the sequential generation of different neural types. They discovered previously unknown temporal transcription factors and characterized their roles in temporal patterning and neuronal specification. The study provides insights into the mechanisms involved in the temporal patterning of neural progenitors.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Michael Ebeid, Ippei Kishimoto, Pooja Roy, Mohd Ali Abbas Zaidi, Alan G. Cheng, Sung-Ho Huh
Summary: This study elucidates the role of beta-Catenin in establishing the identity of inner pillar cells (IPCs) in the mammalian cochlea. The transcriptional function of beta-Catenin is crucial for maintaining IPCs and preventing the formation of extranumerary outer pillar cells (OPCs). Overexpression of beta-Catenin promotes IPC proliferation without generating ectopic IPCs. Supporting cells lacking beta-Catenin transcriptional function show a loss of IPC signatures and gain of OPC signatures. Additionally, targeted deletion of beta-Catenin in IPCs leads to the loss of IPC identity. These findings contribute to future strategies for hair cell regeneration based on IPCs.
Article
Multidisciplinary Sciences
Ksenia Gnedeva, Xizi Wang, Melissa M. McGovern, Matthew Barton, Litao Tao, Talon Trecek, Tanner O. Monroe, Juan Llamas, Welly Makmura, James F. Martin, Andrew K. Groves, Mark Warchol, Neil Segil
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biology
Husniye Kantarci, Yunzi Gou, Bruce B. Riley
Article
Developmental Biology
Rogers M. Brown, Joel C. Nelson, Hongyuan Zhang, Amy E. Kiernan, Andrew K. Groves
DEVELOPMENTAL BIOLOGY
(2020)
Review
Neurosciences
Amrita A. Iyer, Andrew K. Groves
Summary: Non-mammalian vertebrates can naturally restore their auditory and vestibular hair cells by triggering the regeneration of adjacent supporting cells. A key regulator in this process is the transcription factor ATOH1. While ATOH1 has shown the ability to reprogram cochlear non-sensory tissue into hair cell-like cells in young animals, this reprogramming ability diminishes with age.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Litao Tao, Haoze Yu, Juan Llamas, Talon Trecek, Xizi Wang, Zlatka Stojanova, Andrew K. Groves, Neil Segil
Summary: The study reveals that in the mouse inner ear, supporting cells have the potential to transdifferentiate into hair cells during the perinatal period, but this potential is rapidly lost during maturation. Blocking Notch signaling can eliminate epigenetic silencing of hair cell enhancers in supporting cells, allowing them to transdifferentiate into hair cells. This suggests that enhancer decommissioning during cochlear maturation may contribute to the failure of hair cell regeneration in the mature organ of Corti.
DEVELOPMENTAL CELL
(2021)
Article
Neurosciences
Teng-Wei Huang, Amrita A. Iyer, Jeanne M. Manalo, Junsung Woo, Navish A. Bosquez Huerta, Melissa M. McGovern, Heinrich Schrewe, Fredrick A. Pereira, Andrew K. Groves, Kevin K. Ohlemiller, Benjamin Deneen
Summary: Mutations in the Mediator protein complex subunit 12 gene lead to changes in astrocyte morphology, hearing loss, and degeneration of the cochlea in the adult central nervous system. This results in the disruption of auditory function by affecting the structural integrity of the stria vascularis.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Ekin Su Akdemir, Junsung Woo, Navish A. Bosquez Huerta, Brittney Lozzi, Andrew K. Groves, Akdes Serin Harmanci, Benjamin Deneen
Summary: Astrocytes, the most abundant glial cell in the brain, perform various tasks to support neuronal function and circuit activities. Through the study of astrocytes, a unique subpopulation called Lfng-GFP(+) astrocytes was identified, which occupies a distinct anatomic location in the spinal cord and directly contributes to neuronal function and sensory responses.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Hongjie Li, Jasper Janssens, Maxime De Waegeneer, Sai Saroja Kolluru, Kristofer Davie, Vincent Gardeux, Wouter Saelens, Fabrice David, Maria Brbic, Jure Leskovec, Colleen N. McLaughlin, Qijing Xie, Robert C. Jones, Katja Brueckner, Jiwon Shim, Sudhir Gopal Tattikota, Frank Schnorrer, Katja Rust, Todd G. Nystul, Zita Carvalho-Santos, Carlos Ribeiro, Soumitra Pal, Sharvani Mahadevaraju, Teresa M. Przytycka, Aaron M. Allen, Stephen F. Goodwin, Cameron W. Berry, Margaret T. Fuller, Helen White-Cooper, Erika L. Matunis, Stephen DiNardo, Anthony Galenza, Lucy Erin O'Brien, Julian A. T. Dow, Heinrich Jasper, Brian Oliver, Norbert Perrimon, Bart Deplancke, Stephen R. Quake, Liqun Luo, Stein Aerts
Summary: This study presents a single-cell atlas of the fruit fly Drosophila melanogaster, including 580,000 nuclei and annotations of over 250 distinct cell types. It serves as a valuable resource for the Drosophila community and provides a reference for studying genetic perturbations and disease models at single-cell resolution.
Article
Multidisciplinary Sciences
Hsin- Jen, Sunita Singh, Litao Tao, Helen R. Maunsell, Neil Segil, Andrew K. Groves
Summary: GFI1 is a transcription factor that plays a vital role in the differentiation and survival of hair cells in the cochlea. It promotes hair cell differentiation by enhancing ATOH1's transcriptional activity and acts as a direct transcriptional repressor to suppress non-hair cell genes.
SCIENTIFIC REPORTS
(2022)
Article
Allergy
Rajarshi Ghosh, Marita Bosticardo, Sunita Singh, Morgan Similuk, Ottavia M. Delmonte, Francesca Pala, Christine Peng, Colleen Jodarski, Michael D. Keller, Ivan K. Chinn, Andrew K. Groves, Luigi D. Notarangelo, Magdalena A. Walkiewicz, Javier Chinen, Vanessa Bundy
Summary: This study identified heterozygous loss-of-function variants in the FOXI3 gene as a possible genetic basis for nonsevere T-cell lymphopenia. Understanding the genetic etiology of this condition is crucial for clinical management and family planning.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Pei-Ciao Tang, Li Chen, Sunita Singh, Andrew K. Groves, Karl R. Koehler, Xue Zhong Liu, Rick F. Nelson
Summary: In this study, we used stem cell-derived organoids to investigate the effects of Wnt signaling on early placodal ectoderm (PPE) differentiation. We found that modulating Wnt signaling can significantly increase the efficiency and reproducibility of inner ear organoid induction. Our data also reveal the critical role of Wnt signaling in the regionalization of PPE.
Article
Biology
Amrita A. Iyer, Ishwar Hosamani, John D. Nguyen, Tiantian Cai, Sunita Singh, Melissa M. McGovern, Lisa Beyer, Hongyuan Zhang, Hsin- Jen, Rizwan Yousaf, Onur Birol, Jenny J. Sun, Russell S. Ray, Yehoash Raphael, Neil Segil, Andrew K. Groves, Brian S. Kim
Summary: Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed for treating hearing loss. However, the efficiency of hair cell reprogramming declines as the cochlea matures. A combination of ATOH1, GFI1, and POU4F3 can reprogram non-sensory cells of the cochlea to a hair cell fate, but the resulting cells are less mature compared to those generated at an earlier stage. Epigenetic accessibility and signaling from hair cells to supporting cells, including Notch signaling, are key factors that impede hair cell reprogramming in older animals.
Article
Developmental Biology
Ankita Thawani, Helen R. Maunsell, Hongyuan Zhang, Harinarayana Ankamreddy, Andrew K. Groves
Summary: The Foxi3 transcription factor plays an important role in early development by restricting progenitor cells at the neural plate border to a placodal and epidermal fate.
Article
Anatomy & Morphology
Harinarayana Ankamreddy, Ankita Thawani, Onur Birol, Hongyuan Zhang, Andrew K. Groves
Summary: This study successfully traced the development of Foxi3-expressing cells in mice through the introduction of Foxi3(GFP) and Foxi3(CreER) genes, and found that Foxi3 plays a crucial role in craniofacial, inner ear, tooth, and hair development.
DEVELOPMENTAL DYNAMICS
(2023)
Article
Multidisciplinary Sciences
John D. Nguyen, Juan Llamas, Tuo Shi, J. Gage Crump, Andrew K. Groves, Neil Segil
Summary: Mammalian hair cells cannot regenerate in adulthood, but can regenerate in embryonic and neonatal stages through the direct transdifferentiation of neighboring supporting cells. This regeneration potential is lost due to DNA methylation and chromatin accessibility changes in the supporting cells as they mature. Understanding these epigenetic modifications may provide insights for future hearing restoration therapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)