Susan McConnell

Last updated
Susan McConnell
Susan K McConnell.jpg
Born1958
Gary, Indiana
Nationality United States
Alma mater Harvard University
Known for Neural development
Scientific career
Fields Neurobiology
Institutions Stanford University
Doctoral advisor Simon LeVay

Susan McConnell is a neurobiologist who studies the development of neural circuits in the mammalian cerebral cortex. She is a professor in the Department of Biology at Stanford University, where she is the Susan B. Ford Professor of Humanities and Sciences, a Bass University Fellow, and a Howard Hughes Medical Institute Professor. She is an elected member of the National Academy of Sciences and the American Academy of Arts and Sciences.

Contents

Education

McConnell graduated with a joint A.B. degree from Harvard College and Radcliffe College in 1980. She did her doctoral work in the research group of Simon LeVay and received her PhD in neurobiology from Harvard University in 1987. She was a postdoctoral fellow in the laboratory of Carla J. Shatz at Stanford University.

Research

McConnell's research focuses on understanding how neurons in the developing cerebral cortex are produced, differentiated, and connected to form functional circuits.

McConnell's research showed that progression through the cell cycle plays a key role in determining the final differentiated state of a neural progenitor cell. [1] McConnell also confirmed the hypothesis that asymmetric cell division, as determined by the orientation of the dividing progenitor's cleavage plane, regulates cortical development. Her work elucidated the first molecular mechanism for this process, showing that asymmetrically inherited Notch proteins determine whether a new daughter cell will differentiate into a neuron or remain a neural progenitor. [2]

Her work also showed that developing cortical neurons use a variety of different migratory paths as they move from their birthplace to their final destination in the cortex. [3] This work stood in contrast to a prevailing theory at the time, that all neuronal migration in the cortex was dependent upon radial glia.

McConnell's recent work has continued to outline the molecular mechanisms underlying neural differentiation, [4] [5] [6] [7] neuronal migration [8] [9] and axon guidance. [10] [11]

Teaching

Stanford University has recognized McConnell with its two highest teaching honors, the Hoagland Prize for Undergraduate Teaching and the Walter J. Gores Award for Excellence in Teaching. She has taught undergraduate courses on neural development since joining Stanford's faculty in 1989.

From 2010 to 2012, McConnell co-chaired a university-wide commission that evaluated undergraduate education at Stanford. [12] The commission's recommendations encouraged students and teachers "to reconsider what they do, how they do it, and why it matters", [13] and urged reforms to the university's general education programs.

In addition, Dr. McConnell and author Andrew Todhunter were the principal force behind the creation of Stanford's Senior Reflection in Biology, a capstone course for senior undergraduates where life-science students undertake creative projects synthesizing the arts and sciences. [14] [15]

Conservation photography

In addition to her career in research and teaching, McConnell is an accomplished wildlife photographer. After photographing animals during a trip to the Svalbard archipelago in Norway, she developed an interest in using photography to tell stories about animal behavior. [16] [17] She teaches undergraduate classes on conservation photography at Stanford. Her photos have been featured in various publications including Smithsonian [18] and National Geographic . [19]

McConnell was the first non-art Stanford faculty member to have a show in the Stanford Art Gallery. [20] Her show was called On the Shoulders of Giants and focused on elephants, their poaching, and the crisis of the ivory trade. [21]

Personal life

McConnell is married to Richard Scheller, former Chief Scientific Officer and Head of Therapeutics at 23andMe and the former Executive Vice President of Research and Early Development at Genentech.

Awards and honors

McConnell is a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and is a Howard Hughes Medical Institute Professor. She has received many other awards and honors, including:

Related Research Articles

Central nervous system Brain and spinal cord

The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric animals—i.e., all multicellular animals except sponges and jellyfish. It consists of a large nerve running from the superior to the inferior, with the superior end enlarged into the brain. Not all animals with a central nervous system have a brain, although the large majority do.

Cerebral cortex Outer layer of the cerebrum of the mammalian brain

The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of allocortex. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres. The two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system. It plays a key role in attention, perception, awareness, thought, memory, language, and consciousness.

The development of the nervous system, or neural development, or neurodevelopment, refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.

Glia Support cells in the nervous system

Glia, also called glial cells or neuroglia, are non-neuronal cells in the central nervous system and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myelin in the peripheral nervous system, and provide support and protection for neurons. In the central nervous system, glial cells include oligodendrocytes, astrocytes, ependymal cells, and microglia, and in the peripheral nervous system glial cells include Schwann cells and satellite cells. They have four main functions: (1) to surround neurons and hold them in place; (2) to supply nutrients and oxygen to neurons; (3) to insulate one neuron from another; (4) to destroy pathogens and remove dead neurons. They also play a role in neurotransmission and synaptic connections, and in physiological processes like breathing. While glia were thought to outnumber neurons by a ratio of 10:1, recent studies using newer methods and reappraisal of historical quantitative evidence suggests an overall ratio of less than 1:1, with substantial variation between different brain tissues.

Pyramidal cell

Pyramidal cells, or pyramidal neurons, are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cortex and the corticospinal tract. Pyramidal neurons are also one of two cell types where the characteristic sign, Negri bodies, are found in post-mortem rabies infection. Pyramidal neurons were first discovered and studied by Santiago Ramón y Cajal. Since then, studies on pyramidal neurons have focused on topics ranging from neuroplasticity to cognition.

A cortical minicolumn is a vertical column through the cortical layers of the brain. Neurons within the microcolumn "receive common inputs, have common outputs, are interconnected, and may well constitute a fundamental computational unit of the cerebral cortex". Minicolumns comprise perhaps 80–120 neurons, except in the primate primary visual cortex (V1), where there are typically more than twice the number. There are about 2×108 minicolumns in humans. From calculations, the diameter of a minicolumn is about 28–40 μm. Minicolumns grow from progenitor cells within the embryo and contain neurons within multiple layers (2–6) of the cortex.

A cortical column, also called hypercolumn, macrocolumn, functional column or sometimes cortical module, is a group of neurons in the cortex of the brain that can be successively penetrated by a probe inserted perpendicularly to the cortical surface, and which have nearly identical receptive fields. Neurons within a minicolumn (microcolumn) encode similar features, whereas a hypercolumn "denotes a unit containing a full set of values for any given set of receptive field parameters". A cortical module is defined as either synonymous with a hypercolumn (Mountcastle) or as a tissue block of multiple overlapping hypercolumns.

Astrocyte

Astrocytes, also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses.

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.

In developmental psychology and developmental biology, a critical period is a maturational stage in the lifespan of an organism during which the nervous system is especially sensitive to certain environmental stimuli. If, for some reason, the organism does not receive the appropriate stimulus during this "critical period" to learn a given skill or trait, it may be difficult, ultimately less successful, or even impossible, to develop certain associated functions later in life. Functions that are indispensable to an organism's survival, such as vision, are particularly likely to develop during critical periods. "Critical period" also relates to the ability to acquire one's first language. Researchers found that people who passed the "critical period" would not acquire their first language fluently.

Subplate

The subplate, also called the subplate zone, together with the marginal zone and the cortical plate, in the fetus represents the developmental anlage of the mammalian cerebral cortex. It was first described, as a separate transient fetal zone by Ivica Kostović and Mark E. Molliver in 1974.

Radial glial cell Bipolar-shaped progenitor cells of all neurons in the cerebral cortex and some glia

Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and oligodendrocytes. Their cell bodies (somata) reside in the embryonic ventricular zone, which lies next to the developing ventricular system.

Carla J. Shatz American neuroscientist

Carla J. Shatz is an American neurobiologist and an elected member of the American Academy of Arts and Sciences, the American Philosophical Society, the National Academy of Sciences, and the National Academy of Medicine.

The development of the nervous system in humans, or neural development or neurodevelopment involves the studies of embryology, developmental biology, and neuroscience to describe the cellular and molecular mechanisms by which the complex nervous system forms in humans, develops during prenatal development, and continues to develop postnatally.

GPR56

G protein-coupled receptor 56 also known as TM7XN1 is a protein encoded by the ADGRG1 gene. GPR56 is a member of the adhesion GPCR family. Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.

OLIG2

Oligodendrocyte transcription factor (OLIG2) is a basic helix-loop-helix (bHLH) transcription factor encoded by the Olig2 gene. The protein is of 329 amino acids in length, 32kDa in size and contains 1 basic helix-loop-helix DNA-binding domain. It is one of the three members of the bHLH family. The other two members are OLIG1 and OLIG3. The expression of OLIG2 is mostly restricted in central nervous system, where it acts as both an anti-neurigenic and a neurigenic factor at different stages of development. OLIG2 is well known for determining motor neuron and oligodendrocyte differentiation, as well as its role in sustaining replication in early development. It is mainly involved in diseases such as brain tumor and Down syndrome.

EMX1

Homeobox protein EMX1 is a protein that in humans is encoded by the EMX1 gene. The transcribed EMX1 gene is a member of the EMX family of transcription factors. The EMX1 gene, along with its family members, are expressed in the developing cerebrum. Emx1 plays a role in specification of positional identity, the proliferation of neural stem cells, differentiation of layer-specific neuronal phenotypes and commitment to a neuronal or glial cell fate.

TBR1 Protein-coding gene in Homo sapiens

T-box, brain, 1 is a transcription factor protein important in vertebrate embryo development. It is encoded by the TBR1 gene. This gene is also known by several other names: T-Brain 1, TBR-1, TES-56, and MGC141978. TBR1 is a member of the TBR1 subfamily of T-box family transcription factors, which share a common DNA-binding domain. Other members of the TBR1 subfamily include EOMES and TBX21. TBR1 is involved in the differentiation and migration of neurons and is required for normal brain development. TBR1 interacts with various genes and proteins in order to regulate cortical development, specifically within layer VI of the developing six-layered human cortex. Studies show that TBR1 may play a role in major neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and autism spectrum disorder (ASD).

Primary motor cortex

The primary motor cortex is a brain region that in humans is located in the dorsal portion of the frontal lobe. It is the primary region of the motor system and works in association with other motor areas including premotor cortex, the supplementary motor area, posterior parietal cortex, and several subcortical brain regions, to plan and execute movements. Primary motor cortex is defined anatomically as the region of cortex that contains large neurons known as Betz cells. Betz cells, along with other cortical neurons, send long axons down the spinal cord to synapse onto the interneuron circuitry of the spinal cord and also directly onto the alpha motor neurons in the spinal cord which connect to the muscles.

An axo-axonic synapse is a type of synapse, formed by one neuron projecting its axon terminals onto another neuron’s axon.

References

  1. ↑ McConnell, SK; Kaznowski, CE (11 October 1991). "Cell cycle dependence of laminar determination in developing neocortex". Science . 254 (5029): 282–285. Bibcode:1991Sci...254..282M. doi:10.1126/science.1925583. PMID   1925583.
  2. ↑ Chenn, A; McConnell, SK (25 August 1995). "Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis". Cell . 82 (4): 631–641. doi: 10.1016/0092-8674(95)90035-7 . PMID   7664342. S2CID   3200167.
  3. ↑ O'Rourke, NA; Dailey, ME; Smith, SJ; McConnell, SK (9 October 1992). "Diverse migratory pathways in the developing cerebral cortex". Science . 258 (5080): 299–302. Bibcode:1992Sci...258..299O. doi:10.1126/science.1411527. PMID   1411527.
  4. ↑ Hébert, JM; Mishina, Y; McConnell, SK (12 September 2002). "BMP signaling is required locally to pattern the dorsal telencephalic midline". Neuron . 35 (6): 1029–1041. doi: 10.1016/s0896-6273(02)00900-5 . PMID   12354394. S2CID   17084431.
  5. ↑ Alcamo, EA; Chirivella, L; Dautzenberg, M; Dobreva, G; Fariñas, I; Grosschedl, R; McConnell, SK (7 February 2008). "Satb2 regulates callosal projection neuron identity in the developing cerebral cortex". Neuron. 57 (3): 364–377. doi: 10.1016/j.neuron.2007.12.012 . PMID   18255030. S2CID   6716396.
  6. ↑ Chen, B; Wang, SS; Hattox, AM; Rayburn, H; Nelson, SB; McConnell, SK (12 August 2008). "The Fezf2-Ctip2 genetic pathway regulates the fate choice of subcortical projection neurons in the developing cerebral cortex". Proceedings of the National Academy of Sciences of the United States of America . 105 (32): 11382–11387. Bibcode:2008PNAS..10511382C. doi: 10.1073/pnas.0804918105 . PMC   2495013 . PMID   18678899.
  7. ↑ Srinivasan, K; Leone, DP; Bateson, RK; Dobreva, G; Kohwi, Y; Kohwi-Shigematsu, T; Grosschedl, R; McConnell, SK (20 November 2012). "A network of genetic repression and derepression specifies projection fates in the developing neocortex". Proceedings of the National Academy of Sciences of the United States of America. 109 (47): 19071–19078. doi: 10.1073/pnas.1216793109 . PMC   3511157 . PMID   23144223.
  8. ↑ Schaar, BT; Kinoshita, K; McConnell, SK (22 January 2004). "Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons". Neuron. 41 (2): 203–213. doi: 10.1016/s0896-6273(03)00843-2 . PMID   14741102. S2CID   14896246.
  9. ↑ Schaar, BT; McConnell, SK (20 September 2005). "Cytoskeletal coordination during neuronal migration". Proceedings of the National Academy of Sciences of the United States of America. 102 (38): 13652–71365. Bibcode:2005PNAS..10213652S. doi: 10.1073/pnas.0506008102 . PMC   1199551 . PMID   16174753.
  10. ↑ Okada, A; Charron, F; Morin, S; Shin, DS; Wong, K; Fabre, PJ; Tessier-Lavigne, M; McConnell, SK (16 November 2006). "Boc is a receptor for sonic hedgehog in the guidance of commissural axons". Nature . 444 (7117): 369–673. Bibcode:2006Natur.444..369O. doi:10.1038/nature05246. PMID   17086203. S2CID   4412154.
  11. ↑ Chen, B; Schaevitz, LR; McConnell, SK (22 November 2005). "Fezl regulates the differentiation and axon targeting of layer 5 subcortical projection neurons in cerebral cortex". Proceedings of the National Academy of Sciences of the United States of America. 102 (47): 17184–17189. Bibcode:2005PNAS..10217184C. doi: 10.1073/pnas.0508732102 . PMC   1282569 . PMID   16284245.
  12. ↑ "The Study of Undergraduate Education at Stanford" . Retrieved February 28, 2015.
  13. ↑ "The Study of Undergraduate Education at Stanford University" (PDF). Retrieved February 28, 2015.
  14. ↑ "Susan K. McConnell, PhD". Howard Hughes Medical Institute . Retrieved February 27, 2015.
  15. ↑ Peterson, Erin. "Bold Experiments". HHMI Bulletin. Retrieved February 27, 2015.
  16. ↑ Keim, Brandon. "Second Calling". HHMI Bulletin. Retrieved February 27, 2015.
  17. ↑ McConnell, Susan. "In a Last Wild Place". Stanford Alumni Magazine. Retrieved February 27, 2015.
  18. ↑ O'Connell-Rodwell, Caitlin. "How Male Elephants Bond". Smithsonian.com. Smithsonian. Retrieved February 27, 2015.
  19. ↑ Marsh, Laura (2013). Meerkats . National Geographic Children's Books. p.  15. ISBN   978-1426313424.
  20. ↑ University, Stanford (2019-01-30). "Science meets art". Stanford News. Retrieved 2020-07-12.
  21. ↑ "On the Shoulders of Giants - photographs by Susan McConnell | Department of Art & Art History". art.stanford.edu. Retrieved 2020-07-12.
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