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Carole LaBonne | |
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| Alma mater | University of Rochester Harvard University |
| Scientific career | |
| Fields | Developmental and Stem Cell Biology |
| Institutions | California Institute of Technology Northwestern University |
| Website | https://sites.northwestern.edu/labonnelab/ |
Carole LaBonne is a Developmental and Stem Cell Biologist at Northwestern University. She is the Erastus O. Haven Professor of Life Sciences, and Chair of the Department of Molecular Biosciences.
LaBonne received her bachelor's degree from the University of Rochester, [1] doing research with Sayeeda Zain on the molecular basis of Alzheimer's disease. [2] Inspired by the work of famed embryologist and Rochester emeritus professor Johannes Holtfreter, LaBonne pursued doctoral work at Harvard University studying germ layer formation using Xenopus as a model. As a National Science Foundation pre-doctoral Fellow working with Malcolm Whitman, LaBonne characterized the role of FGF signaling in formation of the mesendoderm. During her doctoral study, LaBonne discovered that activin-mediated mesoderm induction required FGF signaling [3] and elucidated the role of RAS-Map Kinase signaling in this process. [4] [5]
Following her graduate work, LaBonne pursued post-doctoral work at the California Institute of Technology as an American Cancer Society Fellow working with Marianne Bronner on the molecular mechanisms underlying the early development of neural crest cells. She showed that formation of neural crest cells, a stem cell population unique to vertebrates, required both attenuation of endogenous BMP signaling and active Wnt signaling, and further showed that up regulation of the zinc-finger transcriptional repressor SNAI2 could bypass the need for BMP inhibition. [6] In subsequent work she demonstrated that Snail-family proteins are required for both establishing the neural crest stem cell state and for the migratory and invasive behavior of neural crest cells, [6] a role these factors also play in metastasizing tumor cells. [7]
LaBonne started her independent laboratory at Northwestern University in 2001 in the department of Molecular Biosciences (formerly Biochemistry, Molecular Biology and Cell Biology). [8] She became a tenured associate professor in 2007, and a full professor in 2012. She was appointed the Erastus O. Haven Professor of Life Sciences in 2017. [9] LaBonne has served as co-leader of the Tumor Environment and Metastasis Program in Northwestern's Robert H. Lurie Comprehensive Cancer Center since 2005. [8] She served as director of Northwestern's Interdisciplinary Biological Sciences PhD program from 2009 to 2017. She currently serves as co-director of the NCI funded Oncogenesis and Developmental Biology Training Program, and as Director of Northwestern's training cluster in Developmental, Systems and Stem Cell Biology. She was appointed Chair of the Department of Molecular Biosciences in 2017. [10] LaBonne has served as the co-director of the Embryology course at the Marine Biological Laboratory since 2020. [11]
Research in the LaBonne laboratory was the first to link Myc to the acquisition of stem cell attributes, and demonstrated that Myc plays a central role in neural crest ontogeny, [12] several years prior to the initial report of the Yamanaka factors. This work proposed that Myc plays this key role in many stem cell populations, and more recent work by others has shown this to be the case. LaBonne's group subsequently demonstrated that Id3 was a key Myc target in maintaining neural crest potency. The growing realization of the commonalities between pluripotent blastula inner cell mass cells/embryonic stem cells and neural crest cells led LaBonne's group to proposed a new model in which neural crest cells arose via retention of the regulatory network controlling pluripotency in blastula cells and showed that neural crest cells possess a previously unrecognized capacity to form endoderm. This pioneering work created a new framework for studying these developmentally and clinically important cells. [13] [14] [15] The LaBonne lab also demonstrated a role for FGF signaling in the retention of pluripotency underling neural crest genesis, and discovered that a novel switching of effector pathways, from Map Kinase to PI3 Kinase, controls the transit from pluripotency to lineage restriction. [16] Recent work in the LaBonne lab has focused on the epigenetic control of pluripotency in naïve blastula cells, including a central role for HDAC activity in both maintaining blastula pluripotency and establishment of the neural crest stem cell population. [17]
Xenopus is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known species of this genus are Xenopus laevis and Xenopus tropicalis, which are commonly studied as model organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects.
Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. However, metabolic composition does get altered quite dramatically where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having the same genome.
Blastulation is the stage in early animal embryonic development that produces the blastula. In mammalian development the blastula develops into the blastocyst with a differentiated inner cell mass and an outer trophectoderm. The blastula is a hollow sphere of cells known as blastomeres surrounding an inner fluid-filled cavity called the blastocoel. Embryonic development begins with a sperm fertilizing an egg cell to become a zygote, which undergoes many cleavages to develop into a ball of cells called a morula. Only when the blastocoel is formed does the early embryo become a blastula. The blastula precedes the formation of the gastrula in which the germ layers of the embryo form.
Gastrulation is the stage in the early embryonic development of most animals, during which the blastula, or in mammals the blastocyst is reorganized into a two-layered or three-layered embryo known as the gastrula. Before gastrulation, the embryo is a continuous epithelial sheet of cells; by the end of gastrulation, the embryo has begun differentiation to establish distinct cell lineages, set up the basic axes of the body, and internalized one or more cell types including the prospective gut.
The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm and endoderm. It emerges and originates from the outer layer of germ cells. The word ectoderm comes from the Greek ektos meaning "outside", and derma meaning "skin".
The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is involved in smell. In humans, it measures 5 cm2 (0.78 sq in) and lies on the roof of the nasal cavity about 7 cm (2.8 in) above and behind the nostrils. The olfactory epithelium is the part of the olfactory system directly responsible for detecting odors.
A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans produce two or three primary germ layers. Some animals, like cnidarians, produce two germ layers making them diploblastic. Other animals such as bilaterians produce a third layer between these two layers, making them triploblastic. Germ layers eventually give rise to all of an animal's tissues and organs through the process of organogenesis.
Organogenesis is the phase of embryonic development that starts at the end of gastrulation and continues until birth. During organogenesis, the three germ layers formed from gastrulation form the internal organs of the organism.
Oct-4, also known as POU5F1, is a protein that in humans is encoded by the POU5F1 gene. Oct-4 is a homeodomain transcription factor of the POU family. It is critically involved in the self-renewal of undifferentiated embryonic stem cells. As such, it is frequently used as a marker for undifferentiated cells. Oct-4 expression must be closely regulated; too much or too little will cause differentiation of the cells.
A neurula is a vertebrate embryo at the early stage of development in which neurulation occurs. The neurula stage is preceded by the gastrula stage; consequentially, neurulation is preceded by gastrulation. Neurulation marks the beginning of the process of organogenesis.
Neural crest cells are a temporary group of cells that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.
Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their function lead to a range of developmental defects. These growth factors typically act as systemic or locally circulating molecules of extracellular origin that activate cell surface receptors. A defining property of FGFs is that they bind to heparin and to heparan sulfate. Thus, some are sequestered in the extracellular matrix of tissues that contains heparan sulfate proteoglycans and are released locally upon injury or tissue remodeling.
In the field of developmental biology, regional differentiation is the process by which different areas are identified in the development of the early embryo. The process by which the cells become specified differs between organisms.
Otic vesicle, or auditory vesicle, consists of either of the two sac-like invaginations formed and subsequently closed off during embryonic development. It is part of the neural ectoderm, which will develop into the membranous labyrinth of the inner ear. This labyrinth is a continuous epithelium, giving rise to the vestibular system and auditory components of the inner ear. During the earlier stages of embryogenesis, the otic placode invaginates to produce the otic cup. Thereafter, the otic cup closes off, creating the otic vesicle. Once formed, the otic vesicle will reside next to the neural tube medially, and on the lateral side will be paraxial mesoderm. Neural crest cells will migrate rostral and caudal to the placode.
SRY -box 2, also known as SOX2, is a transcription factor that is essential for maintaining self-renewal, or pluripotency, of undifferentiated embryonic stem cells. Sox2 has a critical role in maintenance of embryonic and neural stem cells.
Nodal homolog is a secretory protein that in humans is encoded by the NODAL gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta superfamily. Like many other members of this superfamily it is involved in cell differentiation in early embryogenesis, playing a key role in signal transfer from the primitive node, in the anterior primitive streak, to lateral plate mesoderm (LPM).
This article is about the role of Fibroblast Growth Factor Signaling in Mesoderm Formation.
The Spemann-Mangold organizer is a group of cells that are responsible for the induction of the neural tissues during development in amphibian embryos. First described in 1924 by Hans Spemann and Hilde Mangold, the introduction of the organizer provided evidence that the fate of cells can be influenced by factors from other cell populations. This discovery significantly impacted the world of developmental biology and fundamentally changed the understanding of early development.
A developmental signaling center is defined as a group of cells that release various morphogens which can determine the fates, or destined cell types, of adjacent cells. This process in turn determines what tissues the adjacent cells will form. Throughout the years, various development signaling centers have been discovered.
Kristen Kroll is an American developmental and stem cell biologist and Professor of Developmental Biology at Washington University School of Medicine. Her laboratory studies transcriptional and epigenetic regulation of brain development and its disruption to cause neurodevelopmental disorders.
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