About

Laura Gammill, PhD, is an Associate Professor at the University of Minnesota Medical School. Her research focuses on the molecular mechanisms regulating neural crest cell formation, migration, and guidance during embryonic development. She uses chick and mouse embryos to elucidate how neural crest cells become different from their neighbors, migrate over long distances, and form diverse derivatives such as the peripheral nervous system, outflow tract of the heart, and craniofacial skeleton. Her laboratory combines embryological techniques, molecular manipulations, genomic analysis, and proteomics, relying on mouse mutants for genetic functional analyses. This integrative approach aims to provide a clearer understanding of early neural crest development.

Research topics

• Genetics
• Biology
• Cell biology
• Computer Science
• Biochemistry
• Computational biology
• Evolutionary biology

Selected publications

• Preparation and Morphological Analysis of Chick Cranial Neural Crest Cell Cultures

  Journal of Visualized Experiments · 2022-06-27 · 3 citations

  articleSenior author

  During vertebrate development, neural crest cells (NCCs) migrate extensively and differentiate into various cell types that contribute to structures like the craniofacial skeleton and the peripheral nervous system. While it is critical to understand NCC migration in the context of a 3D embryo, isolating migratory cells in 2D culture facilitates visualization and functional characterization, complementing embryonic studies. The present protocol demonstrates a method for isolating chick cranial neural folds to generate primary NCC cultures. Migratory NCCs emerge from neural fold explants plated onto a fibronectin-coated substrate. This results in dispersed, adherent NCC populations that can be assessed by staining and quantitative morphological analyses. This simplified culture approach is highly adaptable and can be combined with other techniques. For example, NCC emigration and migratory behaviors can be evaluated by time-lapse imaging or functionally queried by including inhibitors or experimental manipulations of gene expression (e.g., DNA, morpholino, or CRISPR electroporation). Because of its versatility, this method provides a powerful system for investigating cranial NCC development.

  PublisherDOI

• Preparation and Morphological Analysis of Chick Cranial Neural Crest Cell Cultures

  Journal of Visualized Experiments · 2022-06-27 · 3 citations

  articleSenior author

  During vertebrate development, neural crest cells (NCCs) migrate extensively and differentiate into various cell types that contribute to structures like the craniofacial skeleton and the peripheral nervous system. While it is critical to understand NCC migration in the context of a 3D embryo, isolating migratory cells in 2D culture facilitates visualization and functional characterization, complementing embryonic studies. The present protocol demonstrates a method for isolating chick cranial neural folds to generate primary NCC cultures. Migratory NCCs emerge from neural fold explants plated onto a fibronectin-coated substrate. This results in dispersed, adherent NCC populations that can be assessed by staining and quantitative morphological analyses. This simplified culture approach is highly adaptable and can be combined with other techniques. For example, NCC emigration and migratory behaviors can be evaluated by time-lapse imaging or functionally queried by including inhibitors or experimental manipulations of gene expression (e.g., DNA, morpholino, or CRISPR electroporation). Because of its versatility, this method provides a powerful system for investigating cranial NCC development.

  PublisherDOI

• Extracellular Vesicles and Membrane Protrusions in Developmental Signaling

  Journal of Developmental Biology · 2022 · 13 citations

  Senior authorCorresponding
  • Cell biology
  • Biology
  • Genetics

  During embryonic development, cells communicate with each other to determine cell fate, guide migration, and shape morphogenesis. While the relevant secreted factors and their downstream target genes have been characterized extensively, how these signals travel between embryonic cells is still emerging. Evidence is accumulating that extracellular vesicles (EVs), which are well defined in cell culture and cancer, offer a crucial means of communication in embryos. Moreover, the release and/or reception of EVs is often facilitated by fine cellular protrusions, which have a history of study in development. However, due in part to the complexities of identifying fragile nanometer-scale extracellular structures within the three-dimensional embryonic environment, the nomenclature of developmental EVs and protrusions can be ambiguous, confounding progress. In this review, we provide a robust guide to categorizing these structures in order to enable comparisons between developmental systems and stages. Then, we discuss existing evidence supporting a role for EVs and fine cellular protrusions throughout development.

  PublisherOA PDFDOI

• Chick cranial neural crest cells release extracellular vesicles that are critical for their migration

  Journal of Cell Science · 2022 · 27 citations

  Senior authorCorresponding
  • Biology
  • Cell biology
  • Biochemistry

  The content and activity of extracellular vesicles purified from cell culture media or bodily fluids have been studied extensively; however, the physiological relevance of exosomes within normal biological systems is poorly characterized, particularly during development. Although exosomes released by invasive metastatic cells alter migration of neighboring cells in culture, it is unclear whether cancer cells misappropriate exosomes released by healthy differentiated cells or reactivate dormant developmental programs that include exosome cell-cell communication. Using chick cranial neural fold cultures, we show that migratory neural crest cells, a developmentally critical cell type and model for metastasis, release and deposit CD63-positive 30-100 nm particles into the extracellular environment. Neural crest cells contain ceramide-rich multivesicular bodies and produce larger vesicles positive for migrasome markers as well. We conclude that neural crest cells produce extracellular vesicles including exosomes and migrasomes. When Rab27a plasma membrane docking is inhibited, neural crest cells become less polarized and rounded, leading to a loss of directional migration and reduced speed. These results indicate that neural crest cell exosome release is critical for migration.

  PublisherDOI

• The lysine methyltransferase <scp>SETD2</scp> is a dynamically expressed regulator of early neural crest development

  genesis · 2021-09-09 · 2 citations

  articleSenior authorCorresponding

  SETD2 is a histone H3 lysine 36 (H3K36) tri-methylase that is upregulated in response to neural crest induction. Because the H3K36 di-methylase NSD3 and cytoplasmic non-histone protein methylation are necessary for neural crest development, we investigated the expression and requirement for SETD2 in the neural crest. SetD2 is expressed throughout the chick blastoderm beginning at gastrulation. Subsequently, SetD2 mRNA becomes restricted to the neural plate, where it is strongly and dynamically expressed as neural tissue is regionalized and cell fate decisions are made. This includes expression in premigratory neural crest cells, which is downregulated prior to migration. Likely due to the early onset of its expression, SETD2 morpholino knockdown does not significantly alter premigratory Sox10 expression or neural crest migration; however, both are disrupted by a methyltransferase mutant SETD2 construct. These results suggest that SETD2 activity is essential for early neural crest development, further demonstrating that lysine methylation is an important mechanism regulating the neural crest.

  PublisherDOI

• Profiling NSD3-dependent neural crest gene expression reveals known and novel candidate regulatory factors

  Developmental Biology · 2021 · 11 citations

  Senior authorCorresponding
  • Computer Science
  • Biology
  • Computational biology
  PublisherDOI

• Embryological and Genetic Manipulation of Chick Development

  Methods in molecular biology · 2019-01-01 · 10 citations

  article1st authorCorresponding
  PublisherDOI

• The Society for Craniofacial Genetics and Developmental Biology 40th annual meeting

  American Journal of Medical Genetics Part A · 2018-04-21

  editorial1st author

  None of the authors have a conflict of interest to declare.

  PublisherDOI

• FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation

  Mechanisms of Development · 2014-02-28 · 30 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity

  Molecular Biology of the Cell · 2014-10-16 · 26 citations

  articleOpen accessSenior author

  Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 histone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3-dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3-related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration.

  PublisherOA PDFDOI

Recent grants

• Investigating protein methylation in neural crest development

  NSF · $675k · 2014–2019

• The role of NSD3-mediated protein methylation in neural crest development

  NSF · $458k · 2011–2015

• NIH Grant R03DE023368

  NIH · $228k · 2016

Frequent coauthors

• Julaine Roffers‐Agarwal

  Developmental Studies Center

  24 shared

• Bridget T. Jacques-Fricke

  Hamline University

  10 shared

• Marianne Bronner‐Fraser

  California Institute of Technology

  10 shared

• Callie M. Gustafson

  Developmental Studies Center

  10 shared

• Hazel Sive

  Northeastern University

  7 shared

• Karla J. Hutt

  Monash University

  6 shared

• Katie L. Vermillion

  Morgridge Institute for Research

  4 shared

• Constanza González

  Center for Climate and Resilience Research

  4 shared

Education

• Postdoctoral Fellow and Senior Research Fellow, Biology

  California Institute of Technology

  2006

• PhD, Biology

  Massachusetts Institute of Technology

  1998

• BA, Biological Sciences

  Wellesley College

  1991

Awards & honors

• Dr. James E. Rubin Medical Memorial Award
• Graduating Medical Student Research Award
• Veneziale-Steer Award
• Dr. Marvin and Hadassah Bacaner Research Awards
• Schmidt Steer Award