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Department of Anthropology

Columbian College of Arts & Sciences

Sally A. Moody

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Sally A. Moody

Professor of Anatomy and Regenerative Biology

Contact:

Office Phone: 202-994-2878

Areas of Expertise

Neurobiology; developmental genetics; gene regulatory networks; stem cell biology.

Current Lab Members

Past Lab Members

  • Dr. Tammy Awtry, Postdoctoral Scientist
  • Dr. Daniel Bauer, Internal Medicine, Private practice
  • Dr. Samantha Brugmann, Assistant Professor, Cincinati Children's Hospital
  • Dr. Zoya Demidenko, Research Assistant Professor, NY College of Medicine
  • Dr. Kathleen E. Dennis, Research Scientist, Vanderbuilt University
  • Dr. Betty C. Gallagher, Research Scientist, University of Virginia
  • Dr. Stephen Gee, Postdoctoral Fellow, NIH
  • Dr. Alexandra Hainski-Brousseau, Lecturer, DePaul University, UCLA
  • Dr. Sen Huang, Director, Huang Clinic, Washington, DC
  • Dr. Kristy L. Kenyon, Associate Professor, Hobart and William Smith Colleges
  • Dr. Kathryn B. Moore, Research Associate Professor, University of Utah
  • Dr. Petra D. Pandur, Group Leader, University Ulm, Germany
  • Dr. Steven A. Sullivan, Bioinformatics Specialist, New York University
  • Dr. Norann Zaghloul, Assistant Professor, University of Maryland
  • Bo Yan, M.D., Ph.D., Assistant Research Professor

Current Research

The Role of Maternal Determinant Molecules in Establishing Neural Fates

Using cell lineage analyses, single blastomere transplantation and culture, PCR analyses and gene mis-expression, we showed that dorsal-animal maternal molecules bias one side of the embryo to acquire a dorsal fate shortly after fertilization. Dorsal axis-inducing activity can be activated by an activin-like signal and by localized polyadenylation between the 8- and 16-cell stages. Ventrally localized Wnt8b signaling antagonizes this dorsal-axis activity. Noggin signaling from animal blastomeres promotes a neural fate in vegetal equatorial cells. Recently, we identified 40 unique mRNAs that are enriched in the animal blastomeres using a microarray approach. We are functionally characterizing a number of these to discover whether they bias cells towards a neural fate.

We cloned two maternal genes (foxD5, flotillin1) and are studying their functions in establishing neural fate in dorsal, animal lineages. For a description of FoxD5, please see: A gene regulatory network involved in neural plate development.

Flotillin1 is a member of a family of membrane-associated proteins of unknown function that are highly expressed in the nervous system. These proteins are highly enriched in growing axons. There are three Xenopus alleles (flotillin 1a, 1b, 1c) that have very similar expression profiles. Flotillin1 is expressed during oogenesis and transcripts become enriched in the animal hemisphere precursors of the embryonic ectoderm. Zygotic transcripts are expressed in the presumptive neural plate, with lower levels in the non-neural ectoderm. At neural tube closure, Flotillin1 is expressed in the entire telencephalon, dorsal domains of the rest of the neural tube and dorsal paraxial mesoderm. Primary sensory neurons (Rohon-Beard cells) express Flotillin1 at particularly high levels. At tail bud stages, placodal and branchial arch structures additionally express Flotillin1. While flotillin1 has been implicated in axon regeneration, its function during early development is not known.

Pandur, P.D., M.L. Dirksen, K.B. Moore and S.A. Moody. (2004) Xenopus flotillin1 gene highly expressed in the nervous system and the maternal precursors of the nervous system. Developmental Dynamics 231: 881-887.

A Gene Regulatory Network Involved in Neural Plate Development

In a screen designed to identify animal localized maternal mRNAs (see: "The role of maternal determinant molecules in establishing neural fates" above), we cloned foxD5, which is a member of the forkhead/winged helix transcription factor family. FoxD5 (also known as foxD4L1) is expressed maternally during oogenesis, and maternal transcripts are confined to the animal hemisphere precursors of the embryonic ectoderm. In over-expression and animal cap assays, it activates dorsal axis genes, both neural and muscle, and induces a secondary axis. foxD5 also is expressed zygotically in the presumptive neural ectoderm and neural plate. It is induced strongly by Siamois and Cerberus, but only weakly by neural inducers(Noggin, Chordin). Over-expression assays show that FoxD5 expands Sox2+ neural plate stem cells and represses neural differentiation genes. Its expression is down-regulated as the neural tube closes and differentiation begins. We demonstrated that foxD5 acts upstream of numerous co-expressed neural plate genes, some of which stabilize a neural ectodermal fate and some of which initiate neural differentiation. Together these genes define a regulatory network that establishes the neural ectoderm and controls the onset of neural differentiation.

Specification of Cranial Placode Ectoderm

Placodes are ectodermal specializations in the vertebrate head that contribute to each of the sensory systems (olfactory epithelium, lens, vestibular-acoustic organs and ganglia, cranial ganglia and lateral line). We cloned a member of the Six gene family (six1) that is expressed in the embryonic precursor of the placodes, the pre-placodal ectoderm (PPE). This gene is highly expressed in all neurogenic cranial placodes and lateral line primordia from neurula to tadpole stages.  We used markers of the PPE to show that low concentrations of neural inducers (e.g., Noggin, Chordin) are necessary to induce the PPE and that posteriorizing signals (e.g., Wnt, FGF) repress six1 so it is expressed only in the head. Over-expression of six1 expands the PPE at the expense of neural crest and epidermis, whereas knock-down of Six1 protein results in reduction of the PPE domain and expansion of the neural plate, neural crest and epidermis. Using activator and repressor constructs of six1 or co-expression of wild-type six1 with activating (eya1) or repressing (groucho) co-factors, we demonstrated that Six1 inhibits neural crest and epidermis genes via transcriptional repression and enhances PPE genes via transcriptional activation. Ectopic expression of neural plate, neural crest and epidermal genes in the PPE demonstrates that these factors mutually influence each other to establish the appropriate boundaries between these ectodermal domains. We are continuing to examine the upstream regulators of six1 expression and the down-stream target genes.

In collaboration with Gerhart Schlosser and Mike Klymkowski, we studied whether six1 plays a role in controlling cell proliferation and differentiation during later placode development. six1 is expressed in both superficial and sensorial layers of the neurogenic placodes beginning at mid-gastrula stages, but the neuronal derivatives turn off six1 expression as they migrate away from the placodal region. We showed that both Six1 and Eya1 are required for neural differentiation in all neurogenic placodes. At high levels of expression, Six1 and Eya1 expand the expression of SoxB1 genes, maintain cells in proliferative state and block expression of neuronal differentiation genes. At lower levels, they promote neuronal diferentiation.

The transcriptional activity of Six proteins can be modified by co-factor proteins, the best characterized being Eya and Groucho proteins. We searched the Xenopus genome for orthologues of Drosphila co-factor proteins that interact with the fly six-related factor SO. We identified 33 Xenopus genes with high sequence identity to 20 fly proteins and demonstrate that a large number of these are expressed in cranofacial tissues that express Six1.

Specification of Retinal Stem Cells and Amacrine Cell Phenotypes

The ability of embryonic cells to give rise to the retina is influenced by both maternal molecules and cell-cell interactions throughout development. We demonstrated that maternal asymmetries that set up the three embryonic germ layers (ectoderm, mesoderm, endoderm) influence whether an embryonic cell can give rise to retina. Vegetally localized factors that promote endo-mesoderm formation also antagonize neural and retinal fates involving the Derriere signaling pathway. Those blastomeres that do give rise to the retina are selected from the pool of competent blastomeres by residing in a region of the embryo where BMP signaling is highly repressed.

Using cell lineage analyses, neurotransmitter-specific immunocytochemistry, and confocal microscopy, we determined the cell lineage origin of different neurotransmitter subtypes of amacrine neurons. Using single cell transplantation and gene mis-expression techniques, we demonstrated some of the interactions and transcription factors necessary to produce these specific phenotypes.

The Upstream Regulatory Regions of a Neuron-Specific β-tubulin Gene

By immunocytochemistry we and collaborators showed that the Class III β-tubulin gene is expressed only in neurons beginning at the time that they go through their terminal cell division. Therefore, this gene is likely to be regulated by proteins that establish neuronal cell fate. We cloned the upstream sequences of this gene in rat and analyzed in silico which regions are likely to be involved in neuron-specific expression.

Check out this site to acquire a mammalian neuron-specific anti-beta-tubulin monoclonal antibody.

To acquire the frog neuron-specific anti-beta-tubulin monoclonal antibody, contact Dr. Anthony Frankfurter at the University of Virginia.

To acquire clones of the rat neuron-specific Class III beta-tubulin gene upstream sequences, contact Dr. Moody.

Fate Maps in Xenopus laevis

The first use of intracellular lineage tracers to make fate maps in Xenopus was published by Marcus Jacobson and Giro Hirose (1978, Science 202: 637-639).

The following articles contain the fate maps of Xenopus laevis blastomeres and specific neuronal phenotypes.

Education

BA, Goucher College, 1973
PhD, University of Florida, 1981

Publications

View publications by this faculty member from January 1, 2013 - present.

Rogers, C.D., S.A. Moody and E.S. Casey (2009) “Neural induction and factors that stabilize a neural fate.” Birth Defects Research part C: Embryo Today 87: 249-262. 

Yan, B., K.M. Neilson and S.A. Moody. (2009) Notch signaling downstream of foxD5 promotes neural ectodermal transcription factors that repress neural differentiation. Developmental Dynamics 238: 1358-1365. 

Yan, B., K.M. Neilson and S.A. Moody. (2009) FoxD5 plays a critical upstream role in regulating neural fate and onset of differentiation. Developmental Biology 329: 80-95. 

Yan, B., K.M. Neilson and S.A. Moody. (2010) Microarray identification of novel downstream targets of FoxD5, a critical component of the neural ectodermal transcriptional network. Developmental Dynamics 239: 3467-3480. 

Neilson, K.M., F. Pignoni, B. Yan and S.A. Moody. (2010) Developmental expression patterns of candidate co-factors for vertebrate Six family transcription factors. Developmental Dynamics 239: 3446-3466. 

Gee, S.T., S.L. Milgram, K.L. Kramer, F.L. Conlon and S.A. Moody. (2011) Yes-associated protein 65 (YAP) expands neural progenitors and regulates pax3 expression in the neural plate border zone. PLoS One. 2011;6(6): e20309. Epub 2011 Jun 8". 

Neilson, K.M. and S.A. Moody (2012) “Developmental organogenesis.” In: Regenerative Medicine. (Eds., E. Scott and R. C. Fisher) Jones and Bartlett Publishers LLC., Boston, MA. (in press).

Lee, H.-S., Sokol, S.Y., Moody, S.A, and I. O. Daar (2012) “Using 32-cell stage Xenopus embryos to probe PCP signaling.” In: Methods in Molecular Biology: PCP Methods and Protocols. Humana Press (in press).

Additional publications published before January 1, 2013 may be available within Himmelfarb Library's database.

Classes Taught

ANAT 221 - Advanced Topics in Stem Cell Biology
ANAT 222 - Advanced Research in Stem Cell Biology
BMSC 8212 - Developmental Cell Biology
IDIS 212 - Medical Neurobiology
ANAT 130 - Human Embryology