About

William Talbot is a faculty member in the Department of Developmental Biology at Stanford University, serving as the Faculty Director of the Human Biology program. His role involves overseeing academic and research activities within the program, contributing to the development of curriculum and student engagement in human biology. His background and specific research focus are not detailed on the page, but his position indicates a significant involvement in developmental biology and human biology education at Stanford.

Research topics

• Biochemistry
• Immunology
• Cell biology
• Biology
• Genetics

Selected publications

• In transected nerves, distal repair Schwann cells are required at the injury site to direct and accelerate axonal regrowth

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-18

  articleOpen accessSenior author

  Abstract In vertebrate peripheral nerves, damaged axons can regrow after injury, but the outcomes of regeneration are variable and often incomplete. Schwann cells in injured nerves are important for repair, but their actions at different positions and stages of nerve repair are not well understood. We have investigated the roles of Schwann cells in a larval zebrafish nerve injury model, in which nerves are visible in living animals during development, the initial injury response, and regrowth of the transected axons. After mechanical injury, distal Schwann cells adopt a repair phenotype characterized by changes in marker expression, elongation, and ability to guide axons across the injury site. In contrast, proximal Schwann cells are not sufficient to guide axons across the injury site, and they associate with axons that regrow along aberrant paths. In erbb2 mutants lacking Schwann cells, developmental axon growth is normal, but after transection, axonal regrowth is greatly slowed and often misdirected. By examining animals with nerves partially populated by Schwann cells, we find that axons can regrow through regions devoid of Schwann cells, provided that at least one distal Schwann cell is at the injury site. Timelapse imaging reveals that distal Schwann cells extend processes toward the injury site, which contact and guide axons regrowing from the proximal nerve stump. In irf8 mutants lacking macrophages, debris from transected axons is cleared on schedule, and axonal regrowth is normal. Our studies demonstrate that Schwann cells immediately distal to the injury site have a unique and essential role in axonal regrowth. Main Points After nerve transection in larval zebrafish, proximal and distal Schwann cells have distinct functions at injury site A single distal repair Schwann cell is sufficient for axonal regrowth Axonal regrowth is normal in mutants without macrophages

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• Hogness at one hundred

  Genetics · 2025-08-21 · 1 citations

  articleOpen accessSenior author

  During his remarkable scientific career, David S. Hogness transformed the molecular analysis of genes, genomes, and animal development. Hogness was born 1 century ago this month, on November 17, 1925. On the 100th anniversary of his birth, we would like to share an autobiographical account that Hogness wrote in 1992, 7 years before he retired.

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• Correction to “A cAMP Sensor Based on Ligand-Dependent Protein Stabilization”

  ACS Chemical Biology · 2024-03-08

  erratumOpen accessSenior author

  ADVERTISEMENT RETURN TO ARTICLES ASAPAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to "A cAMP Sensor Based on Ligand-Dependent Protein Stabilization"Mariapaola SidoliMariapaola SidoliMore by Mariapaola Sidoli, Ling-chun ChenLing-chun ChenMore by Ling-chun Chen, Alexander J. LuAlexander J. LuMore by Alexander J. Luhttps://orcid.org/0000-0003-2868-753X, Thomas J. WandlessThomas J. WandlessMore by Thomas J. Wandless, and William S. Talbot*William S. TalbotMore by William S. Talbothttps://orcid.org/0000-0002-2048-7472Cite this: ACS Chem. Biol. 2024, XXXX, XXX, XXX-XXXPublication Date (Web):March 8, 2024Publication History Received20 February 2024Published online8 March 2024https://doi.org/10.1021/acschembio.4c00126© 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0. License Summary*You are free to share (copy and redistribute) this article in any medium or format within the parameters below:Creative Commons (CC): This is a Creative Commons license.Attribution (BY): Credit must be given to the creator.Non-Commercial (NC): Only non-commercial uses of the work are permitted. No Derivatives (ND): Derivative works may be created for non-commercial purposes, but sharing is prohibited. View full license*DisclaimerThis summary highlights only some of the key features and terms of the actual license. It is not a license and has no legal value. Carefully review the actual license before using these materials. This publication is Open Access under the license indicated. Learn MoreArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (650 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

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• The Cl− transporter ClC-7 is essential for phagocytic clearance by microglia

  Journal of Cell Science · 2024 · 9 citations

  Senior authorCorresponding
  • Biology
  • Cell biology
  • Immunology

  Microglia, professional phagocytic cells of the brain, rely upon the appropriate activation of lysosomes to execute their immune and clearance functions. Lysosomal activity is, in turn, modulated by a complex network of over 200 membrane and accessory proteins that relay extracellular cues to these key degradation centers. The ClC-7 chloride (Cl-)-proton (H+) antiporter (also known as CLCN7) is localized to the endolysosomal compartments and mutations in CLCN7 lead to osteopetrosis and neurodegeneration. Although the functions of ClC-7 have been extensively investigated in osteoclasts and neurons, its role in microglia in vivo remains largely unexamined. Here, we show that microglia and embryonic macrophages in zebrafish clcn7 mutants cannot effectively process extracellular debris in the form of apoptotic cells and β-amyloid. Despite these functional defects, microglia develop normally in clcn7 mutants and display normal expression of endosomal and lysosomal markers. We also find that mutants for ostm1, which encodes the β-subunit of ClC-7, have a phenotype that is strikingly similar to that of clcn7 mutants. Together, our observations uncover a previously unappreciated role of ClC-7 in microglia and contribute to the understanding of the neurodegenerative phenotypes that accompany mutations in this channel.

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• Oligodendrocyte development and myelin sheath formation are regulated by the antagonistic interaction between the <scp>Rag‐Ragulator</scp> complex and <scp>TFEB</scp>

  Glia · 2023-09-28 · 6 citations

  articleOpen accessSenior authorCorresponding

  Myelination by oligodendrocytes is critical for fast axonal conduction and for the support and survival of neurons in the central nervous system. Recent studies have emphasized that myelination is plastic and that new myelin is formed throughout life. Nonetheless, the mechanisms that regulate the number, length, and location of myelin sheaths formed by individual oligodendrocytes are incompletely understood. Previous work showed that the lysosomal transcription factor TFEB represses myelination by oligodendrocytes and that the RagA GTPase inhibits TFEB, but the step or steps of myelination in which TFEB plays a role have remained unclear. Here, we show that TFEB regulates oligodendrocyte differentiation and also controls the length of myelin sheaths formed by individual oligodendrocytes. In the dorsal spinal cord of tfeb mutants, individual oligodendrocytes produce myelin sheaths that are longer than those produced by wildtype cells. Transmission electron microscopy shows that there are more myelinated axons in the dorsal spinal cord of tfeb mutants than in wildtype animals, but no significant change in axon diameter. In contrast to tfeb mutants, oligodendrocytes in rraga mutants produce shorter myelin sheaths. The sheath length in rraga; tfeb double mutants is not significantly different from wildtype, consistent with the antagonistic interaction between RagA and TFEB. Finally, we find that the GTPase activating protein Flcn and the RagCa and RagCb GTPases are also necessary for myelination by oligodendrocytes. These findings demonstrate that TFEB coordinates myelin sheath length and number during myelin formation in the central nervous system.

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• Oligodendrocyte Development and Myelin Sheath Formation are Regulated by the Antagonistic Interaction between the Rag-Ragulator Complex and TFEB

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-03-02

  preprintOpen accessSenior authorCorresponding

  Abstract Myelination by oligodendrocytes is critical for fast axonal conduction and for the support and survival of neurons in the central nervous system. Recent studies have emphasized that myelination is plastic and that new myelin is formed throughout life. Nonetheless, the mechanisms that regulate the number, length, and location of myelin sheaths formed by individual oligodendrocytes are incompletely understood. Previous work showed that lysosomal transcription factor TFEB represses myelination by oligodendrocytes and that the RagA GTPase inhibits TFEB, but the step or steps of myelination in which TFEB plays a role have remained unclear. Here, we show that TFEB regulates oligodendrocyte differentiation and also controls the number and length of myelin sheaths formed by individual oligodendrocytes. In the dorsal spinal cord of tfeb mutants, individual oligodendrocytes produce fewer myelin sheaths, and these sheaths are longer than those produced by wildtype cells. Transmission electron microscopy shows that there are more myelinated axons in the dorsal spinal cord of tfeb mutants than in wildtype animals, but no significant change in axon diameter. In contrast to tfeb mutants, oligodendrocytes in rraga mutants produce shorter myelin sheaths. The sheath length in rraga; tfeb double mutants is not significantly different from wildtype, consistent with the antagonistic interaction between RagA and TFEB. Finally, we find that the GTPase activating protein Flcn and the RagCa and RagCb GTPases are also necessary for myelination by oligodendrocytes. These findings demonstrate that TFEB coordinates myelin sheath length and number during myelin formation in the central nervous system. Graphical Abstract

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• A lysosomal regulatory circuit essential for the development and function of microglia

  Science Advances · 2022 · 50 citations

  Senior authorCorresponding
  • Cell biology
  • Biology
  • Genetics

  mutants show increased expression of lysosomal genes but display significant down-regulation of immune- and chemotaxis-related genes. Furthermore, we find that RagA and Folliculin repress the key lysosomal transcription factor Tfeb and its homologs Tfe3a and Tfe3b in the macrophage lineage. Using RNA sequencing, we establish that Tfeb and Tfe3 are required for activation of lysosomal target genes under conditions of stress but not for basal expression of lysosomal pathways. Collectively, our data define a lysosomal regulatory circuit essential for macrophage development and function in vivo.

  PublisherDOI

• Partial loss‐of‐function variant in neuregulin 1 identified in family with heritable peripheral neuropathy

  Human Mutation · 2022-04-29 · 7 citations

  articleOpen accessSenior authorCorresponding

  Neuregulin 1 signals are essential for the development and function of Schwann cells, which form the myelin sheath on peripheral axons. Disruption of myelin in the peripheral nervous system can lead to peripheral neuropathy, which is characterized by reduced axonal conduction velocity and sensorimotor deficits. Charcot-Marie-Tooth disease is a group of heritable peripheral neuropathies that may be caused by variants in nearly 100 genes. Despite the evidence that Neuregulin 1 is essential for many aspects of Schwann cell development, previous studies have not reported variants in the neuregulin 1 gene (NRG1) in patients with peripheral neuropathy. We have identified a rare missense variant in NRG1 that is homozygous in a patient with sensory and motor deficits consistent with mixed axonal and de-myelinating peripheral neuropathy. Our in vivo functional studies in zebrafish indicate that the patient variant partially reduces NRG1 function. This study tentatively suggests that variants at the NRG1 locus may cause peripheral neuropathy and that NRG1 should be investigated in families with peripheral neuropathy of unknown cause.

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• Basic science under threat: Lessons from the Skirball Institute

  Cell · 2022-03-01 · 2 citations

  article
  PublisherDOI

• Promoting validation and cross-phylogenetic integration in model organism research

  Disease Models & Mechanisms · 2022-09-01 · 12 citations

  articleOpen access

  Model organism (MO) research provides a basic understanding of biology and disease due to the evolutionary conservation of the molecular and cellular language of life. MOs have been used to identify and understand the function of orthologous genes, proteins, cells and tissues involved in biological processes, to develop and evaluate techniques and methods, and to perform whole-organism-based chemical screens to test drug efficacy and toxicity. However, a growing richness of datasets and the rising power of computation raise an important question: How do we maximize the value of MOs? In-depth discussions in over 50 virtual presentations organized by the National Institutes of Health across more than 10 weeks yielded important suggestions for improving the rigor, validation, reproducibility and translatability of MO research. The effort clarified challenges and opportunities for developing and integrating tools and resources. Maintenance of critical existing infrastructure and the implementation of suggested improvements will play important roles in maintaining productivity and facilitating the validation of animal models of human biology and disease.

  PublisherDOI

Recent grants

• NIH Grant R01NS065787

  NIH · $1.7M · 2014

• NIH Grant P50HG002568

  NIH · $28.4M · 2014

• NIH Grant R01DK055378

  NIH · $2.5M · 2003

• Genetic Mechanisms of Myelination in Zebrafish

  NIH · $4.9M · 2004–2019

• NIH Grant R56NS050223

  NIH · $390k · 2009

Frequent coauthors

• Alexander F. Schier

  University of Basel

  52 shared

• John H. Postlethwait

  University of Oregon

  30 shared

• Michael A. Gates

  Wellesley College

  23 shared

• Ian G. Woods

  Ithaca College

  20 shared

• Peter D. Kelly

  University College London

  17 shared

• Felicia Chu

  Stanford University

  16 shared

• David S. Hogness

  15 shared

• Hui Huang

  Jiangxi Science and Technology Normal University

  14 shared